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Summary: Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP‐1RAs and developing novel GLP‐1RA‐based co‐agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High‐dose GLP‐1RAs and multi‐hormonal strategies including GLP‐1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high‐dose GLP‐1RAs, unimolecular, and multimolecular GLP‐1R‐based co‐agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP‐1R‐based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide‐spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH. [ABSTRACT FROM AUTHOR]

Introduction: A post hoc analysis of the PIONEER 1–5 and 8 trials assessed the clinically relevant composite endpoints of HbA1c (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. Methods: In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26–78 weeks. This analysis assessed the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. Results: Overall, 3506 people in PIONEER 1–5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p < 0.0001), empagliflozin 25 mg (PIONEER 2, p < 0.0001), sitagliptin 100 mg (PIONEER 3, p < 0.0001) and liraglutide 1.8 mg (PIONEER 4, p < 0.0001). Odds of achieving the composite endpoint of HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment were also significantly greater with orally administered semaglutide versus comparators. Conclusion: In PIONEER 1–5 and 8, odds of achieving clinically relevant reductions in both HbA1c and body weight were significantly greater with orally administered semaglutide versus comparators. [ABSTRACT FROM AUTHOR]

Aims: The aim of this article is to review the safety and efficacy data of dapagliflozin, saxagliptin, and their combination in the management of patients with type 2 diabetes. Evidence for the use of the single-tablet combination formulation is also presented. Methods: A nonsystematic literature review was performed using the Ovid, PubMed, and Google Scholar databases. Results: The addition of dapagliflozin/saxagliptin to metformin can lower mean hemoglobin A1c by as much as 1.47% and lead to weight loss of 0.5-2.0 kg. The risk of genital infections with combination therapy is lower than observed with dapagliflozin alone, suggestive of a protective effect. Adverse event risk at 52-week follow-up was not increased beyond that seen with either monotherapy. Conclusion: Dapagliflozin/saxagliptin combination is generally well tolerated and is an effective tool in helping patients with diabetes improve glycemic control. [ABSTRACT FROM AUTHOR]

The progressive nature of type 2 diabetes necessitates that treatment is intensified as the disease advances. Several studies have shown that basal insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) can be used in combination to successfully improve glycemic control and this combination is increasingly being considered as an alternative to intensification with prandial insulin. Insulin degludec/liraglutide (IDegLira) is the first fixed-ratio combination of a basal insulin and a GLP-1RA in a single formulation. Here we consider the benefits and potential limitations of such a combination, focusing on the unique modes of action of insulin degludec and the once-daily GLP-1RA liraglutide. IDegLira offers an efficacious combination therapy (mean end-of-trial HbA1cwas 6.4–6.9% across the five completed Phase 3 trials), which was well-tolerated in clinical trials. The complementary modes of action resulted in a low rate of hypoglycemia and no weight gain in insulin-treated patients. As a once-daily injection with effects on both fasting and post prandial hyperglycemia, IDegLira has the potential to help many patients reach glycemic target (60–81% of patients achieved HbA1c<7% in clinical trials). [ABSTRACT FROM PUBLISHER]

Individuals can be sent to the Emergency Room (ER) for a variety of reasons. Our goal was to determine the differences in reasons and frequencies for visits to the ER between individuals with and without diabetes. This study was conducted by way of review of ER visit sheets over a three month period at tertiary care centre in Winnipeg, Canada. Examination of the control group (individuals without diabetes) revealed the most common documented reason for ER visits were cardiac complications (49.56%), hypertension (26.25%), renal conditions (15.34%), and neurological complications (5.90%). For the Type 1 diabetes group, reasons for visit to the ER were cardiac complications (33.33%), neurological complications (18.06%), and hypertension, nephropathy, DKA/glycemic control, and infectious diseases (all at 13.89%). Analyzing the documented diagnosis of type 2 individuals revealed similar trends to non-diabetic individuals. Cardiac complications (52.86%) dominated the reasons for admittance to the emergency room, followed by hypertension (32.36%), renal conditions (11.30%), neurological (4.32%), and DKA/glycemic control issues (0.42%), Type 2 diabetes patients presented with similar reasons for visit as patients without diabetes, and thus it appeared as though patients with Type 2 diabetes did not visit the ER primarily due to glycemic control issues. In type 1 diabetes patients, neurological and DKA/glycemic concerns were of higher occurrence than in patients with Type 2 or no diabetes. Cardiovascular, hypertension, and renal concerns constituted major reason for ER visit in all three groups. [ABSTRACT FROM AUTHOR]