Oral Semaglutide in Routine Clinical Practice: Characteristics of People with Type 2 Diabetes Started on the Drug and Changes in Their Clinical Parameters after 24 Weeks of Treatment.

Background/Objectives: Semaglutide is the unique once-daily oral glucagon-like receptor agonist presently available. Aims of this study were to describe clinical characteristics of patients with type 2 diabetes (T2D) initiating oral semaglutide, to assess its effects on glycemic control, body weight (BW) and its tolerability in routine clinical practice. Methods: Electronic medical records from two Italian diabetes clinics were evaluated. Mean glycated hemoglobin (HbA1c) and BW were assessed in adults with T2D before and 6 months after oral semaglutide prescription. Treatment discontinuation and safety data were reported. Results: A total of 192 patients initiating oral semaglutide (44% female) presented a mean age of 66 years, a diabetes duration of 10 years, HbA1c of 7.9% and a BW of 82.6 kg. Almost 50% of patients were obese. Mean HbA1c and BW changes from baseline to follow up were -0.7% and -2.6 kg, respectively. Greater HbA1c reduction was observed in patients with baseline HbA1c ≥ 8% and with diabetes duration <5 years. The composite endpoint of HbA1c ≤7% and a weight loss ≥5% was achieved in 22.5% of the participants. A total of 40 patients (20.8%) discontinued treatment: 26 because of gastrointestinal adverse events, and 10 due to limited effectiveness in lowering HbA1c and/or BW. Conclusions: In a real clinical setting, patients initiating oral semaglutide showed suboptimal metabolic control, short diabetes duration and obesity; a significant improvement in HbA1c and BW was achieved mainly in patients with a more recent diabetes diagnosis, supporting the use of oral semaglutide in the early phase of the disease.

Exenatide Once Weekly: Effectiveness, Tolerability, and Discontinuation Predictors in a Real-world Setting.

PURPOSE: The goal of this study was to evaluate the effectiveness and safety of exenatide once weekly (EOW) and to determine predictors of treatment response and drug discontinuation in patients with type 2 diabetes mellitus (T2DM) followed up for 18 months in a real-world setting. METHODS: This retrospective cohort study included patients with T2DM who initiated EOW 2 mg between 2014 and 2019 in an outpatient diabetes clinic in Italy. Data were collected at baseline and at follow-up visits (6, 12, and 18 months after EOW). We estimated glycosylated hemoglobin (HbA1c) and body weight mean changes from baseline to follow-up visits and assessed the proportion of patients reaching HbA1c target ≤7% and a 5% weight loss after 12 months of treatment. We then attempted to establish predictors of glycemic and weight response, and compared patient characteristics between subjects who persisted on treatment versus those who discontinued EOW. FINDINGS: One-hundred eighty-six patients (46.2% male) were included in the study. The mean (SD) age and diabetes duration were 63.2 (8.9) years and 10.7 years (18.3), respectively. Significant reductions in HbA1c values (-0.9%; 95% CI, -1.1 to -0.8) and body weight (-2.8 kg; 95% CI, -3.4 to -2.2) were observed after 6 months. Sixty-one percent of patients (87 of 143) achieved target HbA1c values ≤ 7% after 12 months, and 34% (45 of 134) exhibited a weight loss of at least 5% of baseline body weight. Blood glucose and weight reductions were maintained after an 18-month follow-up. Predictors of adequate glycemic and weight response were shorter diabetes duration and nonuse of a different GLP-1RA, respectively. Patients on sulfonylureas failed to reach metabolic and body weight targets. The most common adverse events were gastrointestinal side effects (7.5%) and injection site reactions (6.4%), followed by headache (1.1%) and allergic reactions (1.1%). Forty-three percent of patients (79 of 186) discontinued EOW. The main reasons for discontinuation were insufficient HbA1c improvement and/or limited weight reduction (19.9%), side effects (16.1%), or patient decision (6.5%). Predictors of discontinuation were higher HbA1c levels at baseline and use of basal insulin therapy before EOW treatment. IMPLICATIONS: EOW treatment, in a real-world setting, offers sustained and effective glycemic control and weight loss over 18 months in patients with T2DM. Diabetes duration and basal insulin therapy, however, may affect the outcome of EOW treatment, suggesting that early initiation of EOW could improve glycemic control and reduce the risk of treatment discontinuation.

A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile. AREAS COVERED: Adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes. EXPERT OPINION: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a 'similar' safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.

[Type 2 diabetes treatment and cardiovascular risk: what can we learn from trials?] / Trattamento farmacologico del diabete mellito di tipo 2 e rischio cardiovascolare: cosa è possibile capire dai trial?

Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment. Several of such trials have already been performed and their results are available. These results support the cardiovascular safety of three dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin and alogliptin) and of a glucagon-like peptide-1 receptor agonist (GLP-1RA) (lixisenatide). These results, however, also document a plausible protective effect against cardiovascular risk associated with the use of a SGLT2 inhibitor (empagliflozin) and of two GLP-1RAs (liraglutide and semaglutide). Differences and similarities among the results of these cardiovascular safety trials as well as their potential implications will be discussed in this article.