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The progressive nature of Type 2 diabetes necessitates treatment intensification over time in order to maintain glycaemic control, with many patients ultimately requiring insulin therapy. While insulin has unlimited potential efficacy, its initiation is often delayed and improvements in glycaemic control are typically accompanied by weight gain and an increased risk of hypoglycaemia, particularly as HbA1c approaches and falls below target levels. This may account for the sub-optimal control often achieved after insulin initiation. Combining insulin with antihyperglycaemic therapies that have a low risk of hypoglycaemia and are weight-neutral or result in weight loss is a therapeutic strategy with the potential to improve Type 2 diabetes management. Although the effects differ with each individual class of therapy, clinical trials have shown that adding a glucagon-like peptide-1 receptor agonist, dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor to insulin regimens can offer a significant reduction in HbA1c without substantially increasing hypoglycaemia risk, or weight. The evidence and merit of each approach are reviewed in this paper. Once-daily co-formulations of a basal insulin and a glucagon-like peptide-1 receptor agonist have been developed (insulin degludec/liraglutide) or are under development (lixisenatide/insulin glargine). Insulin degludec/liraglutide phase III trials and a lixisenatide/insulin glargine phase II trial have shown robust HbA1c reductions, with weight loss and a low risk of hypoglycaemia. With insulin degludec/liraglutide now approved in Europe, an important consideration will be the types of patients who may benefit most from a fixed-ratio combination; this is discussed in the present review, and we also take a look toward future developments in the field. [ABSTRACT FROM AUTHOR]

Introduction: There is concern that glucagon-like peptide-1 (GLP1) receptor agonists may be associated with acute pancreatitis. The data from the ABCD nationwide liraglutide audit (November 2009–June 2013; 6010 patients) provide an opportunity to assess the extent of the problem in routine clinical practice in the UK. Methods: At every patient visit, audit-contributors were invited to submit, via an electronic form, clinical data collected as part of routine clinical practice, including data on possible side effects of treatment. Cases of 'possible pancreatitis' were identified and we contacted the centres concerned to obtain full details. Results: To date, the audit has monitored 3720 years of exposure to liraglutide. There were four cases of possible pancreatitis documented from the 6010 patients on liraglutide: three patients had likely causes of pancreatitis identified and one patient had no aetiological cause. This sole case represents an incidence of 0.027/100 patient-years of exposure to liraglutide. Conclusion: In cases of acute pancreatitis of a patient on liraglutide, if another cause can be found (usually gall stones associated with obesity), the drug is not be necessarily culpable. People with Type 2 diabetes are at greater risk of acute pancreatitis (hazard ratio between 1.5 and 2.8). Thus, the possibility of liraglutide-associated pancreatitis in 'real-world' clinical practice (0.027/100 patient years) represents a very small risk. [ABSTRACT FROM AUTHOR]

Purpose: Incretin-based medications are a novel class of agents for the treatment of type-2 diabetes mellitus (DM2). The safety profile of these medications is not firmly established, and concerns have been raised about their potential carcinogenicity. The objective of our study was to produce new evidence on the effect of incretin-based medications on cancer risk in patients with DM2., Methods: We conducted a "retrospective cohort" study with data from the Clinical Practice Research Datalink and the Hospital Episodes Statistics in the UK. New users of either an incretin-based medication (n = 18 885) or a sulfonylurea medication (n = 36 929) between 2007 and 2013 were identified and followed for up to 8 years. Cox proportional-hazards models were used to estimate the quasi-intention-to-treat and quasi-per-protocol hazard-ratios for the association between incretin-based medications with cancer while adjusting for potential confounders., Results: The adjusted hazard ratio (95% confidence interval) for use of incretin-based medications versus use of sulfonylurea medications for the overall-cancer outcome was 0.97 (0.90, 1.05) in the quasi-intention-to-treat analysis and 0.90 (0.81, 1.00) in the quasi-per-protocol analysis. In both analyses, the hazard-ratio functions over the 8-year follow-up seemed fairly constant, and the 8-year cumulative-risk functions in the two subcohorts were similar., Conclusions: Our study suggests that the use of incretin-based medications in patients with DM2 does not increase the risk of cancer relative to the use of sulfonylurea medications, at least in the first several years of the use. Further research is needed to assess long-term effects of the use of incretin-based medications on cancer risk., (© 2019 John Wiley & Sons, Ltd.)

Question In patients with {type 2}* diabetes, are incretin-based drugs associated with increased risk for heart failure (HF) compared with combinations of other oral antidiabetic drugs? Methods Design Nested case-control study, using administrative databases in Canada, a general practitioner database linked to hospital data in the UK, and insurance claims data in the USA. ClinicalTrials.gov NCT02456428. Setting Canada (Alberta, Manitoba, Ontario, and Saskatchewan), the UK, and the USA. Patients 1840467 patients ≥18 years of age who had a first-ever prescription for a noninsulin antidiabetic drug at any time were included in the base cohort. Exclusion criteria included previous insulin use. From the base cohort, 1499650 patients were prescribed a new antidiabetic drug after incretin drugs (e.g., dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 analogues) became available and were included in the study cohort (new drug prescription date = baseline), with stratification for previous HF at baseline. Prescriptions could be for new diabetes or for a new drug class in patients already using antidiabetic drugs. 29741 study cohort patients were hospitalized with HF during the study and classified as cases (admission date = case index date): 6536 had previous HF at baseline (mean age 74 y, 59% men, mean treated diabetes duration 1.8 y), and 23205 had no previous HF (mean age 69 y, 57% men, mean treated diabetes duration 0.7 y). Using risk-set sampling, each case was matched with ≤20 controls (n =100480 with previous HF and n =435777 with no previous HF) who were at risk for HF hospitalization at the case index date. Matching was based on age, sex, duration of treated diabetes, baseline date, and duration of follow-up. Risk factors Current use (prescription ongoing or ending ≤30 d before the case index date) of incretin-based drugs, {alone or with other antidiabetic drugs and used as first-, second-, or third-line treatment}*. Because incretins are intended to be second- or third-line drugs, the primary analysis used a reference group of patients using combinations of other oral antidiabetic drugs. Outcome HF hospitalization. Main results The main results are in the Table. Conclusion In patients with type 2 diabetes, incretin-based drugs were not linked to increased risk for heart failure hospitalization compared with combinations of other oral antidiabetic drugs. [ABSTRACT FROM AUTHOR]

The article reports that drug regulators and manufacturers have failed to take action against adverse effects of glucagonlike peptide-1 (GLP-1) based drugs which is being used to treat type 2 diabetes.