Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an important class of drugs with a well-established efficacy and safety profile in patients with type 2 diabetes mellitus. Agents in this class are derived from either exendin-4 (a compound present in Gila monster venom) or modifications of human GLP-1 active fragment. Differences among these drugs in duration of action (ie, short-acting vs long-acting), effects on glycaemic control and weight loss, immunogenicity, tolerability profiles, and administration routes offer physicians several options when selecting the most appropriate agent for individual patients. Patient preference is also an important consideration. The aim of this review is to discuss the differences between and similarities of GLP-1 RAs currently approved for clinical use, focusing particularly on the properties characterising the single short-acting and long-acting GLP-1 RAs rather than on their individual efficacy and safety profiles. The primary pharmacodynamic difference between short-acting (ie, exenatide twice daily and lixisenatide) and long-acting (ie, albiglutide, dulaglutide, exenatide once weekly, liraglutide, and semaglutide) GLP-1 RAs is that short-acting agents primarily delay gastric emptying (lowering postprandial glucose) and long-acting agents affect both fasting glucose (via enhanced glucose-dependent insulin secretion and reduced glucagon secretion in the fasting state) and postprandial glucose (via enhanced postprandial insulin secretion and inhibition of glucagon secretion). Other advantages of long-acting GLP-1 RAs include smaller fluctuations in plasma drug concentrations, improved gastrointestinal tolerability profiles, and simpler, more convenient administration schedules (once daily for liraglutide and once weekly for albiglutide, dulaglutide, the long-acting exenatide formulation, and semaglutide), which might improve treatment adherence and persistence.

Many people with type 2 diabetes mellitus (T2DM) fail to achieve glycaemic control promptly after diagnosis and do not receive timely treatment intensification. This may be in part due to 'clinical inertia', defined as the failure of healthcare providers to initiate or intensify therapy when indicated. Physician-, patient- and healthcare-system-related factors all contribute to clinical inertia. However, decisions that appear to be clinical inertia may, in fact, be only 'apparent' clinical inertia and may reflect good clinical practice on behalf of the physician for a specific patient. Delay in treatment intensification can happen at all stages of treatment for people with T2DM, including prescription of lifestyle changes after diagnosis, introduction of pharmacological therapy, use of combination therapy where needed and initiation of insulin. Clinical inertia may contribute to people with T2DM living with suboptimal glycaemic control for many years, with dramatic consequences for the patient in terms of quality of life, morbidity and mortality, and for public health because of the huge costs associated with uncontrolled T2DM. Because multiple factors can lead to clinical inertia, potential solutions most likely require a combination of approaches involving fundamental changes in medical care. These could include the adoption of a person-centred model of care to account for the complex considerations influencing treatment decisions by patients and physicians. Better patient education about the progressive nature of T2DM and the risks inherent in long-term poor glycaemic control may also reinforce the need for regular treatment reviews, with intensification when required.

Adherence to antihyperglycemic medications is often suboptimal in patients with type 2 diabetes, and this can contribute to poor glycemic control, increased hospitalization, and the development of diabetic complications. Reported adherence rates to antihyperglycemics vary widely among studies, and this may be related to differences in methodology for measuring adherence, patient populations, and other factors. Poor adherence may occur regardless of the specific regimen used and whether therapy is oral or injectable, and can be especially common in chronic, asymptomatic conditions, such as type 2 diabetes. More convenient drug-administration regimens and advances in formulations and delivery devices are among strategies shown to improve adherence to antihyperglycemic therapy, especially for injectable therapy. This is exemplified by technological developments made in the drug class of glucagon-like peptide 1-receptor agonists, which are a focus of this narrative review. Dulaglutide, albiglutide, and prolonged-release exenatide have an extended duration of action and can be administered once weekly, whereas such agents as liraglutide require once-daily administration. The convenience of once-weekly versus once-daily administration is associated with better adherence in real-world studies involving this class of agent. Moreover, provision of a user-friendly delivery device has been shown to overcome initial resistance to injectable therapy among patients with type 2 diabetes. This suggests that recent innovations in drug formulation (eg, ready-to-use formulations) and delivery systems (eg, single-dose prefilled pens and hidden, ready-attached needles) may be instrumental in encouraging patient acceptance. For physicians who aim to improve their patients’ adherence to antihyperglycemic medications, it is thus important to consider the patient’s therapeutic experience (treatment frequency, drug formulation, delivery device). Better adherence, powered by recent technological advances in the delivery of glucagon-like peptide 1-receptor agonists, may thus lead to improved clinical outcomes in type 2 diabetes.

Introduction: The aim of this meta-analysis was to investigate the impact of rapid-acting insulin analogues (RAIAs) and regular human insulin (RHI) on glycemic control, including long-and short-term glycemic variability as Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.10282829.More data are required to assess the relative effects of RAIAs and RHI on glucose control in patients with type 2 diabetes.

Despite the importance of individualised strategies for patients with type 2 diabetes mellitus (T2DM) and the availability of alternative treatments, including glucagonlike peptide-1 receptor agonists (GLP-1 RAs), sulphonylureas are still widely used in practice. Clinical evidence shows that GLP-1 RAs may provide better and more durable glycaemic control than sulphonylureas, with lower risk of hypoglycaemia.Other reported benefits of GLP-1 RAs include weight loss rather than weight gain (as observed with sulphonylureas), blood pressure reduction and improvement in lipid profiles. In general, the main adverse events with GLP-1 RAs are gastrointestinal in nature. The respective modes of action of GLP-1 RAs and sulphonylureas contribute to differences in the durability of glycaemic control (related to effects on beta-cells) and effects on body weight. Moreover, the glucose-dependent mode of action of GLP-1 RAs, which favours a low incidence of hypoglycaemia, contrasts with the glucose-independent mode of action of sulphonylureas. Evidence from cardiovascular outcomes trials indicates a consistent finding of cardiovascular safety across the GLP-1 RAs and suggests a class benefit for the long-acting GLP-1 RAs in reducing three-point major adverse cardiovascular events, cardiovascular mortality and all-cause mortality. In contrast, potential concerns relating to an increased incidence of adverse cardiovascular events with sulphonylureas have yet to be fully resolved. Recent updates to management guidelines recommend that treatment selection for patients with T2DM should consider clinical trial evidence of cardiovascular safety. Available evidence suggests that this selection should give preference to GLP-1 RAs over sulphonylureas, especially for patients at high cardiovascular risk.