Glucose-lowering Medicines For Type 2 Diabetes
Background There is an increasing array of medicines available to improve blood glucose control in type 2 diabetes. Finding the best com-bination for an individual patient requires an assessment of the patient’s characteristics and understanding the mechanism of action for each drug. Objective/s The aim of this article is to provide a rational approach for choosing between the various blood glucose-lowering medicines available for treatment of patients with type 2 diabetes mellitus. Discussion Metformin is the first choice of glucose-lowering medicines for most patients with type 2 diabetes. Sulphonylureas have proven benefits in long-term trials. Insulin is required in patients with symptoms of insulin deficiency. Glucagon-like peptide 1 agonists and sodium-glucose co-transporter 2 inhibitors provide some assistance in weight loss as well as improving blood glucose con-trol. Dipeptidyl peptidase 4 inhibitors provide an alternative to metformin and sulphonylureas, especially when side effects of those drugs limit their use. Re-assessing blood glucose control after an appropriate trial period before deciding on continuing use is appropriate. In recent years, pharmacological options for treating type 2 diabetes have expanded substantially. The place of metformin as the drug of first choice is unquestioned. Sulphonylureas have a long history and their use is supported by outcome data from the UK Prospective Diabetes Study (UKPDS).1 Choosing agents other than metformin or sulphonylureas is more difficult, apart from the use of insulin in patients who are clearly insulin-deficient. Most pharmacological options will reduce glycosylated haemoglobin (HbA1c) by 0.5–1.0%, on average, either as monotherapy, compared to placebo, or in addition to metformin and or a sulphonylure Continue reading >>
Management Of Hyperglycemia In Patients With Type 2 Diabetes And Pre-dialysis Chronic Kidney Disease Or End-stage Renal Disease
Review Metformin-associated Lactic Acidosis: Current Perspectives On Causes And Risk
Abstract Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (< 10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the resu Continue reading >>
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Metformin In Advanced Chronic Kidney Disease: Are Current Guidelines Overly Restrictive?
Nicholas I Cole, Pauline A Swift, Rebecca J Suckling, Peter A Andrews South West Thames Renal Department, Epsom and St Helier University Hospitals, Surrey, UK Address for correspondence: Dr Nicholas Cole Renal Department, St Helier Hospital, Wrythe Lane, Carshalton, Surrey SM5 1AA, UK Tel: +44 (0)7758217166 Fax: +44 (0)2082962857 E-mail: [email protected] Abstract Type 2 diabetes mellitus and chronic kidney disease (CKD) frequently co-exist and the increasing burden of both conditions is a global concern. Metformin is established as the first-line treatment for type 2 diabetes because it is associated with improved cardiovascular outcomes and a reduced risk of hypoglycaemia compared with other treatment options. Patients with CKD may benefit in particular because they are at high risk of both cardiovascular disease and hypoglycaemic episodes. However, the use of metformin is restricted in this population due to the concerns over lactic acidosis. Recent reviews have evaluated this risk and concluded that current guidelines for prescribing metformin in CKD may be too restrictive. This narrative review considers this evidence further, but also examines the strength of evidence that favours the use of metformin in CKD patients. Key words: type 2 diabetes mellitus, chronic kidney disease, metformin, biguanides, lactic acidosis, lactate, cardiovascular disease, hypoglycaemia Introduction Chronic kidney disease (CKD) commonly co-exists with diabetes mellitus; the estimated prevalence of Kidney Disease Outcomes Quality Initiative (KDOQI) stage 3–5 CKD in the UK for those with diabetes is 31%.1 Diabetic nephropathy is the most common attributed cause of end-stage renal disease (ESRD) in those starting dialysis in the UK, with an incidence of 25.4%.2 Overt diabetic nephropat Continue reading >>
Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy
Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring. There was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts. In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing. Continue reading >>
Metformin In People With Kidney Disease
Just over one year ago here at Diabetes Flashpoints, we discussed the possibility that hundreds of thousands of people with both diabetes and kidney disease might benefit from taking the diabetes drug metformin. As we noted then, this drug has carried a “black box” warning on its label — mandated by the U.S. Food and Drug Administration (FDA) — ever since it became available in the United States in 1994, due to concerns about lactic acidosis. This rare but extremely serious reaction was found to be an unacceptably common side effect of a drug related to metformin — phenformin — which was pulled from the U.S. market in 1977. Lactic acidosis is much more common in people with impaired kidney function. Since metformin’s warning label is based, in part, on concerns about a different drug entirely, many researchers have tried to estimate how safe metformin is for people with diabetes whose kidney function is impaired. Last year, we noted that many researchers believe metformin is safe for people with mild to moderate kidney disease, defined as having an estimated glomerular filtration rate (eGFR) of 30–60 ml/min. And one study found that using a safety cutoff of an eGFR of 30 ml/min, nearly one million people in the United States who currently don’t take metformin because of the FDA’s labeling might be able to safely do so. So what’s changed in the last year? The evidence, it seems, has only grown stronger in favor of metformin being more widely prescribed to people with kidney disease. As noted in a recent article at DiabetesInControl.com, the blood-glucose-lowering benefits of loosening restrictions on metformin could be enormous. One study cited in the article, published last August in the journal Diabetes Care, found that depending on how eGFR is ca Continue reading >>
Metformin: The Safest Hypoglycaemic Agent In Chronic Kidney Disease?
Metformin: The Safest Hypoglycaemic Agent in Chronic Kidney Disease? Oxford Kidney Unit, The Churchill Hospital Old Road, Headington, Oxford OX3 7LE (UK) Tel. +44 186 574 3926, E-Mail [email protected] Metformin is the first-line oral agent in the treatment of type 2 diabetes and has many established benefits, including the reduction of macrovascular complications of diabetes. Its prescription in patients with renal impairment is limited by concerns relating to the theoretical risk of lactic acidosis, a fear which is perpetuated by numerous case reports in which it is implicated. Critical review of this literature calls into question the validity of these claims, with metformin usually acting as an innocent bystander in acutely unwell patients with conditions well recognised to precipitate lactic acidosis such as sepsis or hypovolaemia. In fact, the evidence supports the safe use of appropriate doses of metformin in patients with chronic stable renal impairment, and highlights the important possible greater risks of the alternatives, most notably severe hypoglycaemia in patients taking sulphonylureas and/or insulin and fluid retention in patients taking a thiazolidinedione. Other traditional contraindications to metformin use such as heart failure are also being re-evaluated, as the benefits of metformin in these patients are increasingly recognised. Physicians should weigh this evidence carefully before deciding to withdraw metformin therapy in their patients with stable chronic kidney disease. Metformin is a highly effective agent in the treatment of type 2 diabetes. In addition to controlling blood sugar, it has been shown to reduce the long-term complications of diabetes, including macrovascular disease. The longstanding and now entrenched anxiety over th Continue reading >>
Management Of Diabetes Mellitus In Patients With Chronic Kidney Disease
Abstract Glycemic control is essential to delay or prevent the onset of diabetic kidney disease. There are a number of glucose-lowering medications available but only a fraction of them can be used safely in chronic kidney disease and many of them need an adjustment in dosing. The ideal target hemoglobin A1c is approximately 7 % but this target is adjusted based on the needs of the patient. Diabetes control should be optimized for each individual patient, with measures to reduce diabetes-related complications and minimize adverse events. Overall care of diabetes necessitates attention to multiple aspects, including reducing the risk of cardiovascular disease, and often, multidisciplinary care is needed. Introduction Diabetes mellitus is a growing epidemic and is the most common cause of chronic kidney disease (CKD) and kidney failure. Diabetic nephropathy affects approximately 20–40 % of individuals who have diabetes , making it one of the most common complications related to diabetes. Screening for diabetic nephropathy along with early intervention is fundamental to delaying its progression in conjunction with providing proper glycemic control. Given the growing population that is now affected by diabetes and thus, nephropathy, knowledge regarding the safe use of various anti-hyperglycemic agents in those with nephropathy is of importance. In addition, attention to modification of cardiovascular disease (CVD) risk factors is essential. Altogether, knowledge regarding the prevention and management of diabetic nephropathy, along with other aspects of diabetes care, is part of the comprehensive care of any patient with diabetes. Review Recommendations for nephropathy screening in diabetes Patients with diabetes should be screened on an annual basis for nephropathy. I Continue reading >>
Which Diabetes Drug Is Best For Diabetics With Kidney Disease?
Highlights Sitagliptin is as effective as glipizide at lowering blood sugar levels in patients with type 2 diabetes and chronic kidney disease. Sitagliptin is less likely than glipizide to cause dangerously low blood sugar levels. Patients on sitagliptin tend to lose weight, while those on glipizide gain weight. Some blood-sugar-lowering drugs have caused kidney problems in patients with type 2 diabetes, so physicians are especially cautious when prescribing these agents to diabetics who also have chronic kidney disease (CKD). Previous research indicates that the diabetes drugs sitagliptin and glipizide may not cause considerable kidney damage. New clinical trial results presented during the American Society of Nephrology's Annual Kidney Week compared the two drugs. Sitagliptin and glipizide act on different targets but generate the same result--they boost the effects of insulin, which lowers blood sugar levels. Juan Arjona Ferreira, MD, (MSD Corp.) and his colleagues conducted a 54-week study to compare the efficacy and safety of sitagliptin and glipizide in patients with type 2 diabetes and moderate or severe CKD who were not on dialysis. The researchers randomized 426 patients to receive sitagliptin or glipizide. Among the major findings at the end of the study: Blood glucose levels dropped to a similar extent in patients in both groups. Patients receiving sitagliptin were less likely to experience hypoglycemia--or dangerously low blood sugar levels--than patients receiving glipizide (6.2% vs 17.0%). Patients who took sitagliptin tended to lose a small amount of weight, while most patients who took glipizide experienced a slight weight gain. Study authors for "Efficacy and Safety of Sitagliptin vs. Glipizide in Patients with Type 2 Diabetes and Moderate to Severe Chr Continue reading >>
Diabetes Drug Metformin Safe For Patients With Kidney Disease: Review
Alternative medications more costly, have more side effects, researchers say Please note: This article was published more than one year ago. The facts and conclusions presented may have since changed and may no longer be accurate. And "More information" links may no longer work. Questions about personal health should always be referred to a physician or other health care professional. TUESDAY, Dec. 23, 2014 (HealthDay News) -- Although metformin, the popular type 2 diabetes medication, is usually not prescribed for people with kidney disease, a new analysis shows the drug may be safer for these patients than once thought. Metformin has been used in the United States for two decades to help lower blood sugar levels among people with type 2 diabetes. The U.S. Food and Drug Administration cautions that people with kidney disease should not take the drug because it could increase their risk for a potentially serious condition called lactic acidosis. This is when lactic acid builds up in the bloodstream after oxygen levels in the body are depleted. After reviewing published research to evaluate the risks associated with metformin among people with mild to moderate kidney disease, a team of researchers led by Dr. Silvio Inzucchi, a professor of medicine at Yale University, found these patients were at no greater risk for lactic acidosis than people who were not taking the drug. "What we found is that there is essentially zero evidence that this is risky," Inzucchi, who is also medical director of the Yale Diabetes Center, said in a university news release. "The drug could be used safely, so long as kidney function is stable and not severely impaired," he said. Despite warnings, many doctors are already prescribing metformin to patients with kidney disease, the study published Continue reading >>
Should Restrictions Be Relaxed For Metformin Use In Chronic Kidney Disease? No, We Should Never Again Compromise Safety!
Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century. Like other biguanides, metformin can cause a lactic acidosis that is exceptionally rare but fatal. The likelihood of metformin-associated lactic acidosis is substantially higher in patients with kidney impairment and also among those with seemingly normal kidney function who are at risk of acute kidney injury (AKI). Hence, regulatory agencies in many industrialized nations have maintained strict renal restrictions surrounding metformin. However, there have been millions of people exposed to metformin for many years, many of them with serum creatinine values at or close to 1.5 mg/dL with estimated glomerular filtration rates (eGFRs) much below 60 mL/min/1.73 m2 who have not developed lactic acidosis. Thus, there clearly remains controversy in this area, and there has been heightened pressure to remove the renal restrictions of metformin. To provide a discussion on the pros and cons of relaxing the renal restrictions for metformin use, we provide a Point-Counterpoint. In the point narrative below, Drs. Kalantar-Zadeh and Kovesdy provide their argument that although there is little evidence of the potential benefits of metformin in kidney disease, just considering the sheer numbers of metformin users and the high fatality rate of its associated lactic acidosis, the most appropriate practice is to avoid metformin use in people with eGFR <45 mL/min/1.73 m2 or in those who are at high risk of AKI irrespective of underlying eGFR. In the following counterpoint narrative, Drs. Bakris and Molitch argue that the data from a very large analysis demonstrate clearly that serum creatinine should be supplanted with eGFR as the criteria for metformin use and that the incidence Continue reading >>
Renal Side Effects Of Metformin
Metformin, or Glucophage, is a drug commonly used to treat type 2 diabetes mellitus. It is available in both short and long-acting forms. RxList reports the most common side effects associated with metformin, occurring in more than 5 percent of patients using the drug, are diarrhea, nausea, vomiting, flatulence, diffuse lack of strength, headache, indigestion and abdominal discomfort. Metformin-induced renal side effects are rare but can be lethal. Video of the Day Metformin is excreted out of the body by the kidneys. When the kidneys are not functioning properly, metformin can accumulate in high concentrations which may result in lactic acidosis. Lactic acidosis is a rare, serious metabolic abnormality that occurs with uncontrolled diabetes, severe hypotension as well as high metformin levels. According to Drugs.com, metformin-induced lactic acidosis is fatal in more than 50 percent of cases and usually occurs in diabetic patients with significant kidney dysfunction. Metformin should be used with great caution in patients with chronic renal disease and should be temporarily discontinued for surgery or procedures requiring radiocontrast agents. Symptoms of lactic acidosis are usually nonspecific but may include hypothermia, hypotension and a slow heart rhythm. Lactic acidosis always mandates immediate hospitalization with intensive supportive care and usually hemodialysis. Acute Renal Failure Acute renal failure is characterized by the kidneys' inability to filter toxins out of the blood as a result of injury to the kidney. There are numerous causes of acute renal failure but one of the more common is dehydration. Gastrointestinal side effects are common with metformin therapy and significant diarrhea or vomiting, particularly when there is underlying chronic renal dise Continue reading >>
Diabetes Treatment In Patients With Renal Disease: Is The Landscape Clear Enough?
Diabetes treatment in patients with renal disease: Is the landscape clear enough? We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. Diabetes treatment in patients with renal disease: Is the landscape clear enough? Diabetes is the most important risk factors for chronic kidney disease (CKD). The risk of CKD attributable to diabetes continues to rise worldwide. Diabetic patients with CKD need complicated treatment for their metabolic disorders as well as for related comorbidities. They have to treat, often intensively, hypertension, dyslipidaemia, bone disease, anaemia, and frequently established cardiovascular disease. The treatment of hypoglycaemia in diabetic persons with CKD must tie their individual goals of glycaemia (usually less tight glycaemic control) and knowledge on the pharmacokinetics and pharmacodynamics of drugs available to a person with kidney disease. The problem is complicated from the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. This results in fear of use by lack of evidence. Metformin is globally accepted as the first choice in practically all therapeutic algorithms for diabetic subjects. The advantages of metformin are low risk of hypoglycaemia, modest weight loss, effectiveness and low cost. Data of UKPDS indicate that treatment based on metformin results in less total as well cardiovascular mortality. Metformin remains the d Continue reading >>
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Common Oral Diabetes Medications
Disclaimer: This article is for informational purposes only and is not intended to be a substitute for medical advice or diagnosis from a physician. Diabetes is a growing epidemic in the United States and is the number-one cause of chronic kidney disease (CKD) and end stage renal disease (ESRD). Glucose is a major source of energy for the cells in muscles and tissues, including the brain. For glucose to be utilized by these cells, insulin — a hormone secreted by the pancreas — is necessary. A person with diabetes either does not make insulin or is resistant to the insulin his/her body produces, resulting in high blood sugar levels. Type 1 diabetes, also called insulin-dependent diabetes, is caused by the body’s failure to produce insulin and requires insulin injections. People with type 2 diabetes make insulin, but their bodies are resistant to it. Treatment usually comprises of oral diabetes medications, insulin, diet or a combination of these. The following is a list of the most common oral medicines for controlling blood sugar levels. Please note:People with CKD and ESRD should always consult their nephrologist before taking any medications or changing prescribed doses. Sulfonylureas Similar to meglitinides, sulfonylureas stimulate the pancreas to secrete more insulin, but the insulin secretion is not related to increasing blood sugar levels. These drugs are therefore more likely to cause low blood sugar levels or hypoglycemia. Common sulfonylureas are Micronase®(glyburide), Glucotrol®(glipizide) and Amaryl®(glimepiride). Glyburide use should be avoided in patients with severe kidney impairment as defined by a GFR of less than 60 mL/min (CKD stage 3 and below). Because 50 percent of the glyburide is excreted by the kidneys, the drug can build up in people wi Continue reading >>