Metformin is an oral antidiabetic widely used in the treatment of type 2 diabetes mellitus. The best known side effects are gastrointestinal side effects and lactic acidosis; however, vitamin B 12 malabsorption, is less well known. A decrease in vitamin B 12 levels is observed in patients treated with metformin. The mechanism by which this deficit occurs is not clear and it is known to be reversible when treatment is interrupted.

Metformin is an oral antidiabetic widely used in the treatment of type 2 diabetes mellitus. The best known side effects are gastrointestinal side effects and lactic acidosis; however, vitamin B12 malabsorption, is less well known. A decrease in vitamin B12 levels is observed in patients treated with metformin. The mechanism by which this deficit occurs is not clear and it is known to be reversible when treatment is interrupted.

63-year-old diabetic patient whose family physician has requested a blood test to determine vitamin B12 levels.What is the antidiabetic drug he is taking that warrants such a request:

Prescribing of antidiabetic medicines to older diabetes type 2 patients in Lagos, Nigeria.

The incidence of diabetes mellitus in older adults is increasing in Lagos and other parts of Nigeria but there is paucity of information on the use of medicines in this group of patients. A survey was therefore carried out to determine the prevalence of potentially inappropriate prescribing of antidiabetic medications to older diabetes adults in Lagos, Nigeria. A convenient sample of physicians working in seven health care facilities in Lagos were surveyed using a self-administered pre-tested questionnaire to determine the medications they often prescribed for diabetes patients older than 50 years, whether they consider dosage reduction in these patients, and the counselling information they provide to the patients. AGS 2012 Beer's criteria were used to determine potentially inappropriate medication (PIM) for the patients. Factors associated with the tendency to prescribe inappropriately were then evaluated using logistic regression analyses. Glibenclamide, metformin, and metformin/glimepiride combination were regularly prescribed by 45.64-87.25% of the physicians but gliclazide, pioglitazone, pioglitazone/metformin and pioglitazone/glimepiride combinations were prescribed occasionally by 41.61-61.74% of them. Majority of the physicians (87.25%) prescribe glibenclamide to the older patients and do not also always consider dosage reduction on account of older age. Some of these (30.2%) of these physicians equally prescribed chlorpropamide to the patients. Postgraduate qualification was the only significant factor associated with prescription of chlorpropamide (p < 0.05). Inappropriate use of chlorpropamide and glibenclamide, and failure to consider dosage reduction on account of older age have been reported by physicians treating older diabetes patients in Lagos. This calls for continuous education of physicians in Lagos as well as in other parts of Nigeria to promote rational use of antidiabetic medications in the country.

Vitamin B12 deficiency and the knowledge and practice of physicians regarding screening for vitamin B12 deficiency among type 2 diabetic patients on metformin in selected hospitals in Riyadh, Saudi Arabia.

The worldwide prevalence of diabetes is high including Saudi Arabia. One standard first-line treatment for diabetes is metformin, which was reported to increase the risk for vitamin B12 deficiency. We wanted to determine the prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes mellitus patients. We conducted a cross-sectional study at the diabetic clinics of four hospitals in Riyadh, Saudi Arabia. Type 2 diabetes mellitus patients who were on metformin for at least 1 year were included in the study. Associations between B12 deficiency and age, duration of type 2 diabetes mellitus (T2DM), duration of use and dosage of metformin, and use of proton pump inhibitors (PPIs) were determined. Of 363 T2DM patients, 206 (56.7%) were males and 157 (43.3%) were females, mean age was 53.72 ± 11.31 years, the mean duration of T2DM was 9.89 ± 7.32 years, and the mean duration of metformin use was 9.84 ± 7.29 years. There were 205 patients 56.5% who had a daily dose of 750 mg of metformin. The most commonly used oral hypoglycemic agent was gliclizide only in 138 (38.4%) of patients. There were 107 patients (29.5%) who were on PPIs. There were 210 patients (57.9%) who were on vitamin B12 supplementation, of which 111 (30.6%) had a daily dose of 200 mcg. The use of vitamin B12 supplement, duration of T2DM and duration of metformin use was significantly higher among females. The use of vitamin B12 supplement was significant among patients who were 46 years old and above. There were only 16 patients (4.4%) who had available serum vitamin B12 levels. Only 44.0% of the physician respondents know the current recommendation of American Diabetes Association on vitamin B12 screening and supplementation among diabetic patients, and 21.0% never prescribe vitamin B12 to their patients. Routine testing for serum vitamin B12 level is not practiced in our institution. A large percentage of physicians are not aware of the current recommendations of the American Diabetic Association (ADA) regarding vitamin B12 supplementation and screening. Thus, there is a need for doctors involved in the management of diabetes to keep abreast with guidelines and current recommendations and routinely monitor vitamin B12 levels particularly those who were on long-term takers of metformin and the elderly patients to optimize management of diabetes and its complications.

Meglitinide analogues in the treatment of type 2 diabetes mellitus.

Type 2 diabetes mellitus is a complex heterogenous metabolic disorder in which peripheral insulin resistance and impaired insulin release are the main pathogenetic factors. The rapid response of the pancreatic beta-cells to glucose is already markedly disturbed in the early stages of type 2 diabetes mellitus. The consequence is often postprandial hyperglycaemia, which seems to be extremely important in the development of secondary complications, especially macrovascular disease. Therefore one of the main aims of treatment is to minimise blood glucose oscillations and attain near-normal glycosylated haemoglobin levels. Meglitinide analogues belong to a new family of insulin secretagogues which stimulate insulin release by inhibiting ATP-sensitive potassium channels of the beta-cell membrane via binding to a receptor distinct from that of sulphonylureas (SUR1/KIR 6.2). The pharmacokinetic and pharmacodynamic properties of repaglinide, the first drug of these new antihyperglycaemic agents on the market, and of nateglinide, which will be available soon, differ markedly from the currently used sulphonylureas [mainly glibenclamide (glyburide) and glimepiride]. Repaglinide and nateglinide are absorbed rapidly, stimulate insulin release within a few minutes, are rapidly metabolised in the liver and are mainly excreted in the bile. Therefore, following preprandial administration of these drugs, insulin is more readily available during and just after the meal. This leads to a significant reduction in postprandial hyperglycaemia without the danger of hypoglycaemia between meals. The short action of these compounds and biliary elimination makes repaglinide and nateglinide especially suitable for patients with type 2 diabetes mellitus who would like to have a more flexible lifestyle, need more flexibility because of unplanned eating behaviour (e.g. geriatric patients) or in whom one of the other first-line antidiabetic drugs, i.e. metformin, is strictly contraindicated (e.g. nephropathy with creatinine clearance < or = 50 ml/min). Meglitinide analogues act synergistically with metformin and thiazolidinediones (pioglitazone and rosiglitazone) and can be also combined with long-acting insulin (NPH insulin at bedtime). Therefore, these drugs enrich the palette of antidiabetic drugs and make the treatment more flexible and better tolerated, which both add to better metabolic control and support the empowerment and compliance of the patient. However, this will only be the case if the patient and the diabetes care team are trained for this new therapeutic schedule and the healthcare system is able to pay for these rather expensive drugs.

Induction of long-term glycemic control in type 2 diabetic patients using pioglitazone and metformin combination.

To study the effects of pioglitazone and metformin combination in type 2 diabetics in achieving long-term optimal glycemic control. Patients whose duration of type 2 diabetes was less than 24 months were selected for the study. 373 such patients meeting the selection criteria were included in the study and were started on triple drug combination therapy. Three hundred seventy three (183 females and 190 males) patients were initiated on a triple drug combination of gliclazide 80 mg, tid, metformin 500 mg tid and pioglitazone 30 mg od. Once controlled, the doses of gliclazide were reduced if the blood glucose levels decreased. Those patients whose plasma glucose remained in the normal range for more than 6 months without the use of a sulphonylurea were considered to be in pharmacological remission. 48 patients were lost to follow up. At the beginning of the study the pre treatment biochemical parameters in these 325 diabetic patients at the time of enrolment were: average FBG of 209.44+/-73.82 mg/dl, PLBG 294.96+/-107.58 mg/dl, and HbA(1c) 11.21+/-3.85. The post treatment glycemic parameters were: FBG was 124.38+/-40.48 mg/dl (p < 0.0001), and PLBG 162.32+/-54.33 mg/dl (p < 0.001), average glycosylated hemoglobin was 6.45+/-2.17 (p < 0.001). After using the triple drug combination pharmacological remission was achieved in 36.3 percent i.e. 118 (60 males and 58 females) patients. The average time required for achieving remission was 4 (+/-3.3) months in males and 5 (+/-4.02) months in females. 118 patients were maintained remission after 2 years of follow up. The average duration of remission is 27 (+/-2.66) months. There was an average weight gain of 2.56 +/- 1.32 kg in both the groups of patients in remission and those who could not achieve remission. In this study we have found that we could achieve long term glycemic control 'pharmacological remission' in 118 of the 325 patients i.e.36% of type 2 diabetic patients. Insulin sensitizers like pioglitazone along with metformin may induce long-term glycemic control in type 2 diabetic patients.

Drug utilization of oral hypoglycemic agents in a university teaching hospital in India.

India has witnessed a rapidly exploding epidemic of diabetes in recent years and currently leads the world with the largest number of diabetic subjects in a single country. World Health Organization estimates that in 2000, 31.7 million individuals were affected by diabetes in India and these numbers will rise to 79.4 millions by the year 2030. In view of the above situation, drug utilization review of antidiabetic medicines in Indian healthcare settings has a valid significance to promote rational drug use in diabetics. The present study is aimed to determine the drug utilization patterns in type 2 diabetic patients on oral hypoglycemic agents in the Medicine Outpatient Department (OPD) and Inpatient Department (IPD) of Majeedia Hospital, a teaching hospital of Hamdard University, New Delhi. Patients with established type 2 diabetes (n = 218) visiting the OPD and IPD were interviewed using a structured questionnaire during the period January-May 2006. A majority of the type 2 diabetic patients in this setting were treated with multiple antidiabetic drug therapy. The most commonly prescribed antidiabetic drug class was biguanides (metformin) followed by sulphonylureas (glimepiride), thiazolidinediones (pioglitazone), insulin and alpha-glucosidase inhibitors (miglitol). As monotherapy insulin was the most common choice followed by metformin. The most prevalent multiple therapy was a three-drug combination of glimepiride  + metformin + pioglitazone. More than half of the type 2 diabetic patients showed poor adherence (compliance) to the prescribed therapy. This study strongly highlights the need for patient education or counselling on use of antidiabetic and concomitant drugs, monitoring of blood glucose and glycosylated haemoglobin (HbA1c) levels, diet control, and correction of diabetic complications. Metabolic control was poor and HbA1c monitoring was underutilized. Clinical monitoring of patients' adherence to prescribed treatments is recommended and measures should be taken to improve it.

ATC code A10

A10BD Combinations of oral blood glucose lowering drugs A10BD01 Phenformin and sulfonylureas A10BD02 Metformin and sulfonylureas A10BD03 Metformin and rosiglitazone A10BD04 Glimepiride and rosiglitazone A10BD05 Metformin and pioglitazone A10BD06 Glimepiride and pioglitazone A10BD07 Metformin and sitagliptin A10BD08 Metformin and vildagliptin A10BD09 Pioglitazone and alogliptin A10BD10 Metformin and saxagliptin A10BD11 Metformin and linagliptin A10BD12 Pioglitazone and sitagliptin A10BD13 Metformin and alogliptin A10BD14 Metformin and repaglinide A10BD15 Metformin and dapagliflozin A10BD16 Metformin and canagliflozin A10BD17 Metformin and acarbose A10BD18 Metformin and gemigliptin A10BD19 Linagliptin and empagliflozin A10BD20 Metformin and empagliflozin A10BD21 Saxagliptin and dapagliflozin A10BD22 Metformin and evogliptin A10BD23 Metformin and ertugliflozin A10BD24 Sitagliptin and ertugliflozin A10BD25 Metformin, saxagliptin and dapagliflozin A10BD26 Metformin and lobeglitazone

Treatment of type 2 diabetes with a combination regimen of repaglinide plus pioglitazone.

The efficacy and safety of combination therapy (repaglinide plus pioglitazone) was compared to repaglinide or pioglitazone in 24-week treatment of type 2 diabetes. This randomized, multicenter, open-label, parallel-group study enrolled 246 adults (age 24-85) who had shown inadequate response in previous sulfonylurea or metformin monotherapy (HbA(1c) > 7%). Prior therapy was withdrawn for 2 weeks, followed by randomization to repaglinide, pioglitazone, or repaglinide/pioglitazone. In the first 12 weeks of treatment, repaglinide doses were optimized, followed by 12 weeks of maintenance therapy. Pioglitazone dosage was fixed at 30 mg per day. Baseline HbA(1c) values were comparable (9.0% for repaglinide, 9.1% for pioglitazone, 9.3% for combination). Mean changes in HbA(1c) values at the end of treatment were -1.76% for repaglinide/pioglitazone, -0.18% for repaglinide, +0.32% for pioglitazone. Fasting plasma glucose reductions were -82 mg/dl for combination therapy, -34 mg/dl for repaglinide, -18 mg/dl for pioglitazone. Minor hypoglycemia occurred in 5% of patients for the combination, 8% for repaglinide, and 3% for pioglitazone. Weight gains for combination therapy were correlated to individual HbA(1c) reductions. In summary, for patients who had previously failed oral antidiabetic monotherapy, the combination repaglinide/pioglitazone had acceptable safety, with greater reductions of glycemic parameters than therapy using either agent alone.

Prescription of oral antidiabetic drugs in K/DIGO chronic kidney disease stage 3 and 4: a single centre report.

Evaluation of chronic kidney disease (CKD) is essential in order to prescribe properly oral antidiabetic drugs (OADs). The aim of our study was to report hypoglycemic drugs prescription to CKD in a cohort of type 2 diabetes mellitus (DM) outpatients. This survey included 1686 outpatients with type 2 DM treated with OADs who were not taking insulin evaluated by a team of diabetologists. Glomerular filtration rate (GFR) was calculated by the CKD-EPI formula and subjects were classified in the K/DIGO stages. Main clinical parameters were also evaluated. Patients were aged 68±10 years, 57.1% were males, Body Mass Index was 30±5 kg/m2, glycated hemoglobin 8±1%, systolic and diastolic blood pressure values were 138±15/80±9 mmHg. Serum creatinine was 1.03±0.35 mg/dL and GFR 71±21 mL/min/1.73 m2. In 504 patients (30%) GFR was lower than 60 mL/min/1.73 m2. The different treatment groups had different GFR and hypoglycaemic drugs were prescribed differently in the different K/DIGO stages. The majority of subjects in stage 3A and 3B were treated with repaglinide, however a significant percentage of them were treated with metformin and sulfonylureas. Nearly half of subjects with CKD stage 4 were treated with metformin and sulfonylureas. In this report we found that nearly one third of patients with type DM 2 had CKD and in a significant percentage of them OADs were prescribed even if they were in K/DIGO CKD stage 3 and 4.

Beneficial effects of triple drug combination of pioglitazone with glibenclamide and metformin in type 2 diabetes mellitus patients on insulin therapy.

The thiazolidinediones are a class of antidiabetes medication that enhance the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients of type 2 diabetes who are on insulin therapy secondary to failure of routine oral hypoglycemic drugs in controlling their diabetes. To determine the effects of pioglitazone in combination with sulphonylurea and metformin on diabetes control in patients being treated with insulin due to secondary failure of oral hypoglycemic agents. One hundred and twenty-four consecutive type 2 diabetes patients (mean age, 57.13 years) attending four centres in Mumbai, who were being treated with insulin were selected. They were switched on to triple drug combination of glibenclamide 5 mg, metformin 500 mg and pioglitazone 15 mg along with insulin. Study participants were required to have type 2 diabetes mellitus for atleast 5 years. Patients were excluded if they had any of the following: serum creatinine concentration greater than 1.5 mg/dl, alanine aminotransferase (ALT) level more than two times the upper limit of normal, symptomatic angina, cardiac insufficiency or history of myocardial infarction. Pioglitazone 15 mg with glibenclamide 5 mg and metformin 500 mg, significantly decreased hemoglobin HbA1c level from 11.5% to 7.32% (P < 0.001), average fasting blood glucose from 194.8 mg/ dl to 124.06 mg/dl (p < 0.01), average post-prandial blood glucose from 256.24 to 162.32 mg/dl (p < 0.01). At 6 months, 43.35% of patients did not need to be continued on insulin. The total insulin requirement in 124 patients reduced by 71.81%. There were no significant side effects, liver enzymes were within acceptable levels, average weight gain was 2.23 kg, significant hypoglycemia was observed in 28 patients with two requiring hospitalisation, these patients were those who did not stick to follow-up schedules. With proper patient selection, pioglitazone with glibenclamide and metformin can be safely used in patients receiving insulin with good results.

Metformin

Metformin was discovered in 1922. French physician Jean Sterne began the study in humans in the 1950s. It was introduced as a medication in France in 1957 and the United States in 1995. It is on the World Health Organization's List of Essential Medicines. Metformin is the most widely used medication for diabetes taken by mouth. It is available as a generic medication. In 2019, it was the fourth-most commonly prescribed medication in the United States, with more than 85 million prescriptions written for over 17 million patients. Medical uses Metformin is used to lower the blood sugar in those with type 2 diabetes. It is also used as a second-line agent for infertility in those with polycystic ovary syndrome. Type 2 diabetes The American Diabetes Association and the American College of Physicians both recommend metformin as a first-line agent to treat type 2 diabetes. It is as effective as repaglinide and more effective than all other oral diabetes mellitus type 2 drugs.

Patient perceptions of prandial oral therapy for type 2 diabetes.

This survey was conducted to assess patient perceptions of glycemic control, convenience, and flexibility of a prescribed prandial oral therapy for type 2 diabetes mellitus. Questionnaires distributed by physicians yielded baseline responses from 3696 patients who were beginning repaglinide treatment. Data were analyzed from 1233 respondents who also completed follow-up questionnaires after 4 weeks of treatment. Among respondents, 60% were taking repaglinide with other antidiabetic agents in combination therapy; 59% were taking metformin, and 24% were taking troglitazone. Most respondents (84%) indicated that they were "satisfied" or "very satisfied" with repaglinide therapy, 92% wished to continue its use, and 60% believed that the treatment had improved their attitude toward taking antidiabetic medication. Patients perceived that fasting blood glucose levels were reduced during treatment, as was the incidence of hyperglycemia. Corresponding changes in perceived frequency of hypoglycemia during repaglinide treatment were minimal. Patient perceptions of prandial oral therapy with repaglinide were predominantly positive, due mostly to the perception that glucose control was achieved, with minimal perception of any increase in hypoglycemic episodes.

Alström syndrome

Antibiotics: patients with lung problems will be prescribed antibiotics because they are more prone to infections like bronchitis. Oral diabetes medications: are taken by mouth to treat diabetes. Can be taken combined into a single pill, which may be more effective and convenient for people with diabetes. It is usually taken once or twice daily before meals. Some of these medications includes: Meglitinides (repaglinide and nateglinide): taken to stimulate the cells found in the pancreas to release insulin. These drugs are taken by mouth daily before each meal and could cause a drop in blood sugar. Metformin (biguanide): decreases the amount blood sugar being released by the liver and by stimulating the cells within muscles to take up blood sugar. Taken twice daily. Thiazolidinediones (rosiglitazone and pioglitazone): taken to help insulin work more efficiently in muscle and fat cells causing the liver to release less glucose. Is associated with heart failure.

Diabetes medication

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are useful only in type 2 diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old who have had diabetes mellitus for under ten years. They cannot be used with type 1 diabetes, or diabetes of pregnancy. They can be safely used with metformin or glitazones. The primary side-effect is hypoglycemia. Typical reductions in glycated hemoglobin (A1C) values for second-generation sulfonylureas are 1.0–2.0%. First-generation agents tolbutamide acetohexamide tolazamide chlorpropamide Second-generation agents glipizide glyburide or glibenclamide glimepiride gliclazide glyclopyramide gliquidone Nonsulfonylurea secretagogues Meglitinides

Diabetes and Aging: From Treatment Goals to Pharmacologic Therapy.

Diabetes is becoming one of the most widespread health burning problems in the elderly. Worldwide prevalence of diabetes among subjects over 65 years was 123 million in 2017, a number that is expected to double in 2045. Old patients with diabetes have a higher risk of common geriatric syndromes, including frailty, cognitive impairment and dementia, urinary incontinence, traumatic falls and fractures, disability, side effects of polypharmacy, which have an important impact on quality of life and may interfere with anti-diabetic treatment. Because of all these factors, clinical management of type 2 diabetes in elderly patients currently represents a real challenge for the physician. Actually, the optimal glycemic target to achieve for elderly diabetic patients is still a matter of debate. The American Diabetes Association suggests a HbA1c goal <7.5% for older adults with intact cognitive and functional status, whereas, the American Association of Clinical Endocrinologists (AACE) recommends HbA1c levels of 6.5% or lower as long as it can be achieved safely, with a less stringent target (>6.5%) for patients with concurrent serious illness and at high risk of hypoglycemia. By contrast, the American College of Physicians (ACP) suggests more conservative goals (HbA1c levels between 7 and 8%) for most older patients, and a less intense pharmacotherapy, when HbA1C levels are ≤6.5%. Management of glycemic goals and antihyperglycemic treatment has to be individualized in accordance to medical history and comorbidities, giving preference to drugs that are associated with low risk of hypoglycemia. Antihyperglycemic agents considered safe and effective for type 2 diabetic older patients include: metformin (the first-line agent), pioglitazone, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists. Insulin secretagogue agents have to be used with caution because of their significant hypoglycemic risk; if used, short-acting sulfonylureas, as gliclazide, or glinides as repaglinide, should be preferred. When using complex insulin regimen in old people with diabetes, attention should be paid for the risk of hypoglycemia. In this paper we aim to review and discuss the best glycemic targets as well as the best treatment choices for older people with type 2 diabetes based on current international guidelines.

Pioglitazone

Given previous experiences with the related drug troglitazone, acute diseases of the liver are regarded as a contraindication for pioglitazone. Side effects A press release by GlaxoSmithKline in February 2007 noted that there is a greater incidence of fractures of the upper arms, hands and feet in female diabetics given rosiglitazone compared with those given metformin or glyburide. The information was based on data from the ADOPT trial. Following release of this statement, Takeda Pharmaceutical Company, the developer of pioglitazone (sold as Actos in many markets) admitted that it has similar implications for female patients. The risk of hypoglycemia is low in the absence of other drugs that lower blood glucose.

Adulteration of herbal antidiabetic products with undeclared pharmaceuticals: a case series in Hong Kong.

The current study aims to examine the problem of adulteration of herbal antidiabetic products with undeclared pharmaceuticals, including both registered and banned drugs. All cases involving use of adulterated herbal antidiabetic products referred to a tertiary centre for clinical toxicology analysis from 2005 to 2010 inclusive were retrospectively reviewed. The patients' demographic characteristics, clinical presentations, medical history, drug history and the analytical findings of the herbal antidiabetic products were studied. A total of 27 cases involving use of 29 adulterated herbal antidiabetic products were identified. Seventeen of the patients (63%) had clinical toxicities associated with the illicit products. Hypoglycaemia was the most common adverse effect, followed by lactic acidosis. Analysis of the 29 illicit herbal antidiabetic products revealed eight undeclared registered or banned oral antidiabetic agents, namely glibenclamide (n= 22), phenformin (n= 18), metformin (n= 6), rosiglitazone (n= 6), gliclazide (n= 2), glimepiride (n= 2), nateglinide (n= 1) and repaglinide (n= 1). Non-antidiabetic drugs were also detected in some products. Up to four adulterants were detected within the same product. Adulteration of herbal antidiabetic products with undeclared pharmaceuticals is a significant yet under-recognized problem. Patients taking these illicit products could be at risk of potentially fatal adverse effects. It is important to educate the public to avoid taking pCMs of dubious source. Effective regulatory measures should be put in place to address the problem.

Managing diabetes in India: paradigms in care--outcomes and analysis in a comprehensive, clinical practice survey of Indian physicians.

Diabetes continues to be a pandemic despite huge strides in the awareness and management of the condition. The incidence of diabetes has been projected to rise by almost 170% in most of the developing countries including India. Currently, about 50 million people suffer from diabetes in India with the figures expected to reach 87 million by the year 2030. To assess the management trends in India, a cross-section of doctors across all the major zones of the country were requested to answer a set of questions based on a case profile. Approximately 1000 doctors from all corners of India provided their feedback on various issues of diabetes management. The patient profile was that of an overweight 46-year-old Indian female with hypertension, diabetes and dyslipidaemia with a history of recurrent urinary tract infection (UTI). Almost 84.5% of doctors concurred with the diagnosis of metabolic syndrome for this patient. The awareness about diabetes being a comorbidity as well as a cause for recurrent UTI was high with 86% of doctors choosing diabetes as a cause for recurrent UTI. Around 94% of doctors chose metformin as the drug of choice for the management of this patient. A total of 74% of doctors chose the combination of metformin and sulfonylurea for the management of postprandial hyperglycaemia. Opinions were divided on the choice of drugs for the management of diabetes in a non-obese patient with 31% of doctors still choosing metformin as the drug of choice as per the American Diabetes Association 2009 guidelines and 66% of doctors choosing glimeperide as the first choice in a non-obese patient in concordance with the Association of Physicians of India/Indian College of Physicians (API/ICP) guidelines on diabetes. However, 95% of doctors unanimously chose metformin as the drug of choice in patients with abdominal obesity and diabetes. Almost 83% of doctors were aware that Indians have a genetic predisposition to diabetes due to an inherently smaller beta cell mass associated with insulin resistance. Majority of the physicians were also aware of the adverse effects of most of the antidiabetic drugs with 86% of the physicians identifying hydrochlorothiazide as the cause of worsening uric acid levels in diabetics, when used for the management of hypertension. Practice patterns in India generally conform to guidelines. The survey also demonstrated that majority of the physicians are aware of the different complexities associated with the management of diabetes.

Diabetes medication

Generic Many anti-diabetes drugs are available as generics. These include: Sulfonylureas – glimepiride, glipizide, glyburide Biguanides – metformin Thiazolidinediones (Tzd) – pioglitazone, Actos generic Alpha-glucosidase inhibitors – Acarbose Meglitinides – nateglinide Combination of sulfonylureas plus metformin – known by generic names of the two drugs No generics are available for dipeptidyl peptidase-4 inhibitors (Januvia, Onglyza), the glifozins, the incretins and various combinations. Alternative Medicine The effect of Ayurvedic treatments has been researched, however due to methodological flaws of studies it has not been possible to draw conclusion regarding efficacy of these treatments and there is insufficient evidence to recommend them. References Further reading Anti-diabetic drugs

Pioglitazone/glimepiride

Medical uses In the United States pioglitazone/glimepiride is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a thiazolidinedione and sulfonylurea or who have inadequate glycemic control on a thiazolidinedione alone or a sulfonylurea alone. In the European Union pioglitazone/glimepiride is indicated for the treatment of people with type 2 diabetes mellitus who show intolerance to metformin or for whom metformin is contraindicated and who are already treated with a combination of pioglitazone and glimepiride. References External links Anti-diabetic drugs

Pioglitazone/metformin

Pioglitazone/metformin, sold under the brand name Actoplus Met among others, is a fixed-dose combination anti-diabetic medication used to improve glycemic control in adults with type 2 diabetes. It contains pioglitazone, a thiazolidinedione, and metformin, a biguanide. Mechanisms Pioglitazone is a member of the thiazolidinedione class, it decreases insulin resistance in the periphery and in the liver resulting in increased insulin dependent glucose disposal and decreased hepatic glucose output. Metformin is a member of the biguanide class, improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

Pioglitazone

Medical uses Pioglitazone is used to lower blood glucose levels in type 2 diabetes either alone or in combination with a sulfonylurea, metformin, or insulin. While pioglitazone does decrease blood sugar levels, the main study that looked at the medication found no difference in the main cardiovascular outcomes that were looked at. The secondary outcome of death from all causes, myocardial infarction, and stroke were lower. Pioglitazone has been found to reduce all-cause mortality in type 2 diabetic patients compared to other therapies, with a 60% reduction in mortality in those exposed to pioglitazone, compared to those never exposed. Another study found an all-cause mortality hazard ratio of 0.33 for pioglitazone after adjusting for >40 covariates, compared to insulin.

Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus.

Repaglinide, a carbamoylmethyl benzoic acid derivative, is the first of a new class of oral antidiabetic agents designed to normalise postprandial glucose excursions in patients with type 2 diabetes mellitus. Like the sulphonylureas, repaglinide reduces blood glucose by stimulating insulin release from pancreatic beta-cells, but differs from these and other antidiabetic agents in its structure, binding profile, duration of action and mode of excretion. In clinical trials of up to 1-year's duration, repaglinide maintained or improved glycaemic control in patients with type 2 diabetes mellitus. In comparative, 1-year, double-blind, randomised trials (n = 256 to 544), patients receiving repaglinide (0.5 to 4mg before 3 daily meals) achieved similar glycaemic control to that in patients receiving glibenclamide (glyburide) < or = 15 mg/day and greater control than patients receiving glipizide < or = 15 mg/day. Changes from baseline in glycosylated haemoglobin and fasting blood glucose levels were similar between patients receiving repaglinide and glibenclamide in all studies; however, repaglinide was slightly better than glibenclamide in reducing postprandial blood glucose in I short term study (n = 192). Patients can vary their meal timetable with repaglinide: the glucose-lowering efficacy of repaglinide was similar for patients consuming 2, 3 or 4 meals a day. Repaglinide showed additive effects when used in combination with other oral antidiabetic agents including metformin, troglitazone, rosiglitazone and pioglitazone, and intermediate-acting insulin (NPH) given at bedtime. In 1-year trials, the most common adverse events reported in repaglinide recipients (n = 1,228) were hypoglycaemia (16%), upper respiratory tract infection (10%), rhinitis (7%), bronchitis (6%) and headache (9%). The overall incidence of hypoglycaemia was similar to that recorded in patients receiving glibenclamide, glipizide or gliclazide (n = 597) [18%]; however, the incidence of serious hypoglycaemia appears to be slightly higher in sulphonylurea recipients. Unlike glibenclamide, the risk of hypoglycaemia in patients receiving repaglinide was not increased when a meal was missed in 1 trial. In conclusion, repaglinide is a useful addition to the other currently available treatments for type 2 diabetes mellitus. Preprandial repaglinide has displayed antihyperglycaemic efficacy at least equal to that of various sulphonylureas and is associated with a reduced risk of serious hypoglycaemia. It is well tolerated in a wide range of patients, including the elderly, even if a meal is missed. Furthermore, glycaemic control is improved when repaglinide is used in combination with metformin. Thus, repaglinide should be considered for use in any patient with type 2 diabetes mellitus whose blood glucose cannot be controlled by diet or exercise alone, or as an adjunct in patients whose glucose levels are inadequately controlled on metformin alone.

[Starting insulin or not? And if so, which basal insulin?]

A 55-year-old patient with a BMI of 30 kg/m2 is referred for uncontrolled type 2 diabetes mellitus. His HbA1c-concentration is 71 mmol/mol, despite an initial 8% weight loss and treatment with metformin and glimepiride. The general practitioner proposes to start with insulin, but the patient refuses. We discuss whether there is a good alternative for insulin such as more weight loss and the addition of more drugs. Our patient then changes his mind and agrees to start insulin treatment. Basal insulin is usually recommended in cases like this.Since there are no significant differences between different types of available basal insulin, it seems reasonable to take price into account. Our patient achieved reasonable glucose control without weight gain using a combination of basal insulin and a GLP-1 receptor agonist.

Metformin

It was withdrawn from the market in the UK and India in 2010, and in New Zealand and South Africa in 2011. From November 2011 until November 2013 the FDA did not allow rosiglitazone or metformin/rosiglitazone to be sold without a prescription; moreover, makers were required to notify patients of the risks associated with its use, and the drug had to be purchased by mail order through specified pharmacies. In November 2013, the FDA lifted its earlier restrictions on rosiglitazone after reviewing the results of the 2009 RECORD clinical trial (a six-year, open-label randomized control trial), which failed to show elevated risk of heart attack or death associated with the medication. Pioglitazone The combination of metformin and pioglitazone (Actoplus Met, Piomet, Politor, Glubrava) is available in the US and the European Union. DPP-4 inhibitors Dipeptidyl peptidase-4 inhibitors inhibit dipeptidyl peptidase-4 and thus reduce glucagon and blood glucose levels.

Effects of early use of pioglitazone in combination with metformin in patients with newly diagnosed type 2 diabetes.

Type 2 diabetes is characterised by a progressive decline in HbA1c control over time. Early combination therapy, rather than sequential introduction of individual oral glucose-lowering agents, has been proposed to prevent this gradual rise in HbA1c. This observational study assessed the effect of early dual combination oral glucose-lowering therapies within 6 months of diagnosis in newly diagnosed, drug-naïve patients with type 2 diabetes. This was an observational, open-label, non-randomised study in newly diagnosed patients with type 2 diabetes, aged 35-70 years, with HbA1c levels > 8.0% at diagnosis or > 7.0% at the 3-6-month follow-up. Patients were allocated to dietary management alone if the HbA1c level was 7.0-8.0% at diagnosis. Metformin combined with gliclazide, repaglinide, or pioglitazone was given at diagnosis if the HbA1c was > 8.0%. Similar treatments were introduced at 3-6 months if the HbA1c was > 7.0%. Over a 3-year period, HbA1c was measured at 3-monthly intervals. All patients underwent regular dietetic review. Target HbA1c was < or = 7.0%. 416 patients were considered eligible for inclusion, with a mean (+/- SD) age of 54.1 +/- 9.2 years, BMI of 33.5 +/- 6.1 kg/m2, and baseline HbA1c of 8.6 +/- 1.7%. A mixed model analysis of variance on the 178 patients who started with combination therapy, either immediately or after a 3-6 month period on diet, showed that metformin plus gliclazide, repaglinide, or pioglitazone was associated with a gradual increase in HbA1c values. Amongst those patients treated with the metformin/pioglitazone combination there was an estimated 0.1% increase in HbA1c/year. This was much less pronounced than the rises seen in HbA1c/year of 0.5% with the metformin/gliclazide and metformin/repaglinide combinations. This preliminary analysis of an observational, non-randomised, open-label ongoing study has shown that early use of combination therapy at time of diagnosis or within the first 3-6 months following diagnosis with metformin plus pioglitazone in newly diagnosed type 2 diabetes results in a slower deterioration in glycaemic control than that with metformin combined with either gliclazide or repaglinide. This may be due to the beta-cell protective properties of pioglitazone. These results need to be confirmed by further studies with a more robust design and methodology.

[A case of an elderly diabetic patient with dementia effectively treated with weekly exenatide].

A 74-year-old man with diabetes mellitus since 64 years of age had been treated with glimepiride, metformin and alogliptin; however, his glycemic control remained poor, i.e., a casual blood glucose level of 318 mg/dl, HbA1c level of 10.6% and glycated albumin level of 24.9%. Although his blood glucose level improved with intensive insulin therapy, he exhibited dementia with an MMSE score of 9/30 and was unable to continue insulin injections by himself, thus rejecting his family's help. The extended-release form of the GLP-1 agonist exenatide (Bydureon(®)) was recently introduced in Japan. This new anti-diabetic agent enables the administration of once-weekly type 2 diabetes treatment that delivers a continuous dose of exenatide in a single weekly injection. We employed weekly exenatide therapy in combination with oral hypoglycemic agents in this case. The patient visited our outpatient clinic for injections every week, showing a remarkable improvement in his HbA1c level, from 10.7% to 7.1% in five months. Subcutaneous induration was the only side effect of weekly exenatide injection. Weekly exenatide therapy can be easily managed by other caregivers and is expected to be a useful treatment approach in elderly diabetic patients with dementia.

Pioglitazone/metformin

Indication Pioglitazone/metformin is indicated as an adjunct to diet and exercise: To improve glycemic control in patients with type 2 diabetes, or For patients who are already treated with a separate combination of pioglitazone and metformin, For patients whose diabetes is not adequately controlled with metformin alone, or For patients who have initially responded to pioglitazone alone and require additional glycemic control. Dosage and administration Use in pregnancy and lactation Pioglitazone/metformin should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women with combination of pioglitazone and metformin or its individual components. It is not known whether pioglitazone and/or metformin are secreted in human milk. Because many drugs are excreted in human milk, pioglitazone/metformin should not be administered to a breastfeeding woman.

Getting to goal in newly diagnosed type 2 diabetes using combination drug "subtraction therapy".

The treatment of newly diagnosed type 2 diabetes mellitus is diverse, with no clear consensus regarding the initial drug regimen or dosing to achieve optimal glycemic control. We treated 44 consecutive patients with newly diagnosed type 2 diabetes with maximally tolerated doses of pioglitazone 45 mg/day, metformin 1000-2000 mg/day, and repaglinide 1-4 mg before meals. The doses and drugs were subsequently decreased ("subtraction therapy") to achieve optimal glycemic control and minimize side effects. Three primary outcomes were measured: the short term HbA1c response, the long term HbA1c response, and the incidence of hypoglycemia. All 44 patients responded with a rapid, progressive decline in their HbA1c levels from 11.43±2.3% to 6.17±0.72% (101±25.1 mmol/mol to 44±7.9 mmol/mol) by three months, and remained stable thereafter. An HbA1c ≤7.0% (≤53 mmol/mol) was reached within 1-4 months in 42 of 44 patients, and in every patient by 12 months. Each patient's lowest HbA1c level, 5.65±0.6% (38±6.6 mmol/mol), was reached over 6.3±2.9 months. Patients with initial HbA1c levels >10% (>86 mmol/mol) (n=33) responded similarly as those with HbA1c levels <10% (<86 mmol/mol) (n=11). Combination drug therapy maintained HbA1c levels between 5.0 and 7.0% (31 and 53 mmol/mol) for up to 14.83 years. Only one clinically significant hypoglycemic event occurred during 261.08 person-years of follow-up. In our experience, combination drug "subtraction therapy" was safe and effective for treating all newly diagnosed type 2 diabetic patients.

Vitamin B12

Metformin Reduced serum levels of vitamin B12 occur in up to 30% of people taking long-term anti-diabetic metformin. Deficiency does not develop if dietary intake of vitamin B12 is adequate or prophylactic B12 supplementation is given. If the deficiency is detected, metformin can be continued while the deficiency is corrected with B12 supplements. Other drugs Certain medications can decrease the absorption of orally consumed vitamin B12, including: colchicine, extended-release potassium products, and antibiotics such as gentamicin, neomycin and tobramycin. Anti-seizure medications phenobarbital, pregabalin, primidone and topiramate are associated with lower than normal serum vitamin concentration. However, serum levels were higher in people prescribed valproate. In addition, certain drugs may interfere with laboratory tests for the vitamin, such as amoxicillin, erythromycin, methotrexate and pyrimethamine. Chemistry

Longitudinal assessment of the quality of life and patterns of antidiabetic medication use in patients with type 2 diabetes, Saudi Arabia perspective, DISCOVER study.

Patients with type 2 diabetes nowadays have a wide range of new antidiabetic medications with better efficacy and safety. Physicians' attitude toward selecting antidiabetic medications to reach targeted glycemic control and better quality of life (QOL) has not been studied prospectively. The global DISCOVER study aims to comprehensively provide a real-world assessment of the treatment pattern changes for patients with type 2 diabetes, in addition to QOL assessment. The Kingdom of Saudi Arabia was one of the countries participating in the DISCOVER study program. This study is a part of the prospective, longitudinal multinational DISCOVER study conducted in 38 countries including Saudi Arabia, a country facing an epidemic of type 2 diabetes, recruited 519 adult patients with type 2 diabetes with a mean age of 52.4 ± 11 years, where, they were followed up for three years period, where 477 patients completed the follow-up period. The clinical, biochemical, and patient lifestyle data were assessed periodically during the study period. DISCOVER study is registered with ClinicalTrials.gov identifiers: NCT02322762. The most frequently used antidiabetic medications (ADMs) initially and during the follow-up were biguanides (metformin) and sulfonylureas (gliclazide, glibenclamide, glimepiride, glipizide, and glyclopyramide). Insulin (premix Insulin, basal insulin, and basal/bolus insulin) and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, and linagliptin) were the most frequent second and alternative of therapy. Other medications namely thiazolidinediones (TZds) (pioglitazone and rosiglitazone), incretins (exenatide and liraglutide), and Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (canagliflozin) were used at a lesser rate. Drug availability, efficacy, and safety were the main determinants for choosing antidiabetic medications. The physical component score of the QOL had shown a significant decrease, while the mental component score has demonstrated an increase in QOL using SF36v2 Survey. There is an increasing trend of using of newly available ADMs, mainly DPP-4 inhibitors. The major limitation of ADMs use is related to efficacy, availability, and safety. This warrant taking all the measures to overcome these limitations through adopting a multidisciplinary team approach for close monitoring of the patients and any unfavorable side effects. Additionally, global insurance coverage for all patients with type 2 diabetes could be a solution for the drug availability factor.

Glimepiride: evidence-based facts, trends, and observations (GIFTS). [corrected].

Type 2 diabetes mellitus is characterized by insulin resistance and progressive β cell failure; therefore, β cell secretagogues are useful for achieving sufficient glycemic control. Glimepiride is a second-generation sulfonylurea that stimulates pancreatic β cells to release insulin. Additionally, is has been shown to work via several extra pancreatic mechanisms. It is administered as monotherapy in patients with type 2 diabetes mellitus in whom glycemic control is not achieved by dietary and lifestyle modifications. It can also be combined with other antihyperglycemic agents, including metformin and insulin, in patients who are not adequately controlled by sulfonylureas alone. The effective dosage range is 1 to 8 mg/day; however, there is no significant difference between 4 and 8 mg/day, but it should be used with caution in the elderly and in patients with renal or hepatic disease. In clinical studies, glimepiride was generally associated with lower risk of hypoglycemia and less weight gain compared to other sulfonylureas. Glimepiride use may be safer in patients with cardiovascular disease because of its lack of detrimental effects on ischemic preconditioning. It is effective in reducing fasting plasma glucose, post-prandial glucose, and glycosylated hemoglobin levels and is a useful, cost-effective treatment option for managing type 2 diabetes mellitus.

InternalMed_Harrison

follow-up by the health care provider, possibly in the presence of a caregiver. Chlorpropamide has a prolonged half-life, particularly in older adults, and should be avoided because it is associated with a high risk of hypoglycemia. Metformin should be used with caution and only in patients free of severe renal insufficiency. Renal insufficiency should be assessed by a calculated glomerular filtration rate or, in very old patients who have reduced muscle mass, by a direct measure of creatinine clearance from a 24-h urine collection. Lifestyle changes in diet and exercise and a little weight loss can prevent or delay diabetes in high-risk individuals and are substantially more effective than metformin treatment. The risk of type 2 diabetes decreased by 58% in a study of diet and exercise, and this effect was similar at all ages and in all ethnic groups. The risk reduction with standard care plus metformin was 31%.