Empagliflozin: Role in Treatment Options for Patients with Type 2 Diabetes Mellitus.

Empagliflozin is an oral treatment for type 2 diabetes mellitus (T2DM), one of the leading causes of death in the US and around the world. Recently, the EMPA-REG OUTCOME study has shown that empagliflozin added to standard of care treatment reduced the risk of cardiovascular (CV) events in patients with T2DM who were also at increased CV risk. The risk of major adverse CV events (MACE: first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke) was reduced by 14% relative to placebo (HR 0.86; 95.02% CI: 0.74-0.99; P = 0.04 for superiority). The risk of CV death was reduced by 38% relative to the placebo group (HR 0.62; 95% CI: 0.49-0.77; P < 0.001) and the risk of death from any cause by 32% (HR 0.68; 95% CI: 0.57-0.82; P < 0.001). Furthermore, empagliflozin was associated with reduced risk of hospitalization for heart failure and of renal adverse events. As well as EMPA-REG OUTCOME, empagliflozin has been studied in a number of clinical trials in patients with T2DM, in various combinations, including with insulin. Empagliflozin has shown significant improvements in glycemic control, body weight, and blood pressure, albeit improvements are limited in patients with declining renal function (estimated glomerular filtration rate <45 ml/min/1.73 m2). Empagliflozin has been generally well tolerated, with the typical adverse events of genital mycotic infections usually being straightforward to manage. Considering all the data together, empagliflozin appears to be a promising option for many patients with T2DM, but care will still be needed to ensure that use is appropriate for an individual patient's characteristics.

Lixisenatide: A New Member of the Glucagon-Like Peptide 1 Receptor Agonist Class of Incretin Therapies.

In Brief In the past decade, various incretin-based therapies have emerged in clinical practice. These drugs, including dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists lower A1C with weight-neutral or weight-lowering effects and a relatively lower risk of hypoglycemia. This article provides a review of lixisenatide, a once-daily GLP-1 receptor agonist for the treatment of type 2 diabetes.

Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes.

DESCRIPTION: The American Diabetes Association (ADA) published the 2016 Standards of Medical Care in Diabetes (Standards) to provide clinicians, patients, researchers, payers, and other interested parties with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. METHODS: The ADA Professional Practice Committee performed a systematic search on MEDLINE to revise or clarify recommendations based on new evidence. The committee assigns the recommendations a rating of A, B, or C, depending on the quality of evidence. The E rating for expert opinion is assigned to recommendations based on expert consensus or clinical experience. The Standards were reviewed and approved by the Executive Committee of the ADA Board of Directors, which includes health care professionals, scientists, and laypersons. Feedback from the larger clinical community was incorporated into the 2016 revision. RECOMMENDATIONS: The synopsis focuses on 8 key areas that are important to primary care providers. The recommendations highlight individualized care to manage the disease, prevent or delay complications, and improve outcomes.

The importance of postprandial glycemic control: optimizing add-on therapy to basal insulin.

Diabetes, mainly type 2 diabetes mellitus (T2DM), is associated with a growing clinical and economic burden in the United States, which is expected to increase in association with an aging population. Sufficient glycemic control in patients with T2DM, in order to reduce the risk of micro- and macrovascular complications associated with diabetes, is mediated by lifestyle modifications and a regimen of increasingly intensive antidiabetes drugs. Several treatments and strategies are available for primary care physicians to select from when choosing the most appropriate therapy for their individual patients with T2DM, but, ultimately, due to the progressive nature of the disease, most of these patients will require insulin therapy to maintain glycemic control. Regimens containing basal and postprandial insulins are widely used, but there is still widespread reluctance to initiate insulin treatment due to fear of weight gain and hypoglycemia. Furthermore, as patients approach recommended glycated hemoglobin targets, postprandial hyperglycemia becomes the main contributor to hyperglycemic exposure, necessitating the timely initiation of prandial treatment. Finally, insulin treatment can be limited by factors like the number of injections, mealtime restrictions, complex titration algorithms and patient adherence. Recent developments in antidiabetes drug research have brought more convenient basal and postprandial regimens closer. Clinical evaluation of the efficacy and safety of basal insulins plus add-on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has yielded promising results. Primary care physicians are continually challenged to optimize insulin treatment strategies to maximize patient outcomes. Emerging strategies such as long-acting basal insulin analogs and short-acting GLP-1 RAs are particularly appealing to address this challenge.

User's guide to mechanism of action and clinical use of GLP-1 receptor agonists.

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are injectable glucose-lowering medications approved for the treatment of adult patients with type 2 diabetes mellitus (T2DM). This article provides practical information to guide primary care physicians on the use of GLP-1RAs in patients with T2DM. Two short-acting (once- or twice-daily administration; exenatide and liraglutide) and three long-acting (weekly administration; albiglutide, dulaglutide and exenatide) GLP-1RAs are currently approved in the US. These drugs provide levels of GLP-1 receptor agonism many times that of endogenous GLP-1. The GLP-1RAs have been shown to significantly improve glycemic parameters and reduce body weight. These agents work by activating GLP-1 receptors in the pancreas, which leads to enhanced insulin release and reduced glucagon release-responses that are both glucose-dependent-with a consequent low risk for hypoglycemia. Effects on GLP-1 receptors in the CNS and the gastrointestinal tract cause reduced appetite and delayed glucose absorption due to slower gastric emptying. The most common adverse effects are gastrointestinal, which are transient and less common with the long-acting drugs. GLP-1RAs are recommended as second-line therapy in combination with metformin, sulfonylureas, thiazolidinediones or basal insulin, providing a means of enhancing glucose control while offsetting the weight gain associated with insulin and some oral agents. GLP-1RAs represent a useful tool that the primary care physician can use to help patients with T2DM achieve their therapeutic goals.

Weight change in patients with type 2 diabetes starting basal insulin therapy: correlates and impact on outcomes.

BACKGROUND: An increase in body weight is a commonly perceived effect of insulin therapy for type 2 diabetes mellitus, and this may serve as a barrier to insulin initiation and usage. OBJECTIVE: To investigate the baseline clinical and demographic factors associated with weight gain during insulin glargine therapy, and the implications of weight change on clinical outcomes. METHODS: This was a retrospective analysis of patient-level data from phase 3 or 4 randomized controlled, treat-to-target (fasting plasma glucose [FPG] ≤ 100 mg/dL) trials evaluating basal insulin glargine for ≥ 24 weeks. The Pearson correlation coefficient and Cochran-Armitage trend statistic were used to calculate the existence of a trend between absolute and relative weight change, and relative glycated hemoglobin (HbA1c) change from baseline; likelihood of achieving target HbA1c < 7.0%; change from baseline FPG; insulin dose requirements; incidence of hypoglycemia; and adverse events. RESULTS: Eleven studies were included, encompassing a total of 2140 patients. Patients starting insulin glargine treatment gained a mean ± standard deviation 1.8 ± 3.7 kg (4.0 ± 8.2 lb). Most patients had limited weight change (± 2.5 kg or 5.5 lb). Younger age, higher baseline HbA1c, and higher baseline FPG were predictive of greater weight gain (P < 0.0001). Those who gained more weight experienced the largest decrease from baseline in HbA1c and FPG. More weight gain was associated with higher insulin dose requirements, an increased risk of experiencing either symptomatic or glucose-confirmed (< 70 mg/dL) hypoglycemia, and more adverse events. Older patients (> 65 years) were less likely to gain weight or to experience glucose-confirmed hypoglycemia, but more likely to experience severe hypoglycemia. CONCLUSIONS: In this retrospective analysis of patient-level data, most patients had a stable weight (defined as ± 2.5 kg) after 24 weeks of insulin glargine, and weight gain varied with patient demographics. Therefore, insulin glargine can be used in these patient groups with type 2 diabetes without expectation of significant weight gain.