A Network Meta-Analysis Comparing Semaglutide Once-Weekly with Other GLP-1 Receptor Agonists in Japanese Patients with Type 2 Diabetes

Diabetes Ther https://doi.org/10.1007/s13300-018-0397-1 ORIGINAL RESEARCH A Network Meta-Analysis Comparing Semaglutide Once-Weekly with Other GLP-1 Receptor Agonists in Japanese Patients with Type 2 Diabetes Neil Webb . Michelle Orme . Michal Witkowski . Rie Nakanishi . Jakob Langer Received: January 19, 2018 Ó The Author(s) 2018 M. Orme ICERA Consulting Ltd., Swindon, UK on diet and exercise, who have previously received 0–1 oral antidiabetic drugs (OADs). Data at 52–56 weeks were extracted for the following outcomes (feasible for analysis in an NMA): glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, systolic blood pressure (SBP), and overall hypoglycemia. The data were synthesized using an NMA and a Bayesian framework. Results: Four trials, identified from the SR and Japanese-specific searches, were relevant for inclusion in the NMA. When compared to dulaglutide 0.75 mg QW, semaglutide 0.5 mg QW was shown to provide significant reductions in HbA1c [- 0.61% (12.3 mmol/mol)], weight (- 1.45 kg), SBP (- 5.03 mmHg), and FPG (- 1.26 mmol/L). No significant differences in the proportion of patients achieving a HbA1c level \ 7% (53 mmol/mol) or the risk of overall hypoglycemia were observed between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. Conclusion: Overall, semaglutide 0.5 mg QW was associated with significant reductions from baseline in HbA1c, weight, SBP, and FPG compared with dulaglutide 0.75 mg QW in Japanese patients with T2DM. These data may provide valuable evidence for clinical decision-making, cost-effectiveness analyses, and health technology appraisal (HTA) requirements. Funding: Novo Nordisk Pharma Ltd. R. Nakanishi
J. Langer (&) Novo Nordisk Pharma Ltd., Tokyo, Japan e-mail: Keywords: Dulaglutide; GLP-1 receptor agonist/analogue; Glycemic control; HbA1c; ABSTRACT Introduction: Semaglutide once-weekly (QW) is a novel glucagon-like peptide-1 (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to-head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs) in a Japanese population, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of semaglutide QW vs GLP-1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on the comparison between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. Methods: A systematic review (SR) and supplementary Japanese searches were conducted to identify trials of GLP-1 RAs in Japanese patients Enhanced content To view enhanced content for this article go to https://doi.org/10.6084/m9.figshare.59195 14. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13300018-0397-1) contains supplementary material, which is available to authorized users. N. Webb
M. Witkowski DRG Abacus, Bicester, Oxfordshire, UK Diabetes Ther Indirect comparison; Japan/Japanese; Network meta-analysis; Semaglutide; Type 2 diabetes; Weight INTRODUCTION Type 2 diabetes mellitus (T2DM) is characterized by increased insulin insensitivity coupled with a progressive failure of pancreatic b-cells, resulting in a gradual loss of glycemic control and hyperglycemia [1]. If uncontrolled, hyperglycemia can lead to diabetic complications, including microvascular (e.g., retinopathy) and macrovascular (e.g., myocardial infarction) complications [2]. Globally, the prevalence of diabetes is increasing and it is estimated that 642 million people aged 20–79 years will have diabetes by 2040; of these people, 87–91% will have T2DM [3]. In Japan, a national survey has shown that the prevalence of diabetes has increased from 8.9 million in 2007 to 10 million in 2016 [4]. Specifically, a significant increase in the prevalence of T2DM has also been recorded in a cohort study [5]; this study attributed the increase in T2DM to higher rates of obesity and reduced physical activity levels [5]. Treatment for T2DM is focused on the management of hyperglycemia and reducing the levels of glycated hemoglobin (HbA1c) [6]; the reduction in HbA1c is associated with a reduction in the risk of diabetic complications [2, 7]. In Japan, the main HbA1c target set by the Japanese Diabetes Society is \ 7% (53.0 mmol/mol), which was established from the perspective of preventing complications [8]. However, despite the wide range of treatments available, a recent survey has shown that 47% of patients with T2DM in Japan do not achieve the recommended HbA1c goal [9]. In addition, patients with a higher body mass index (BMI) were less likely to achieve the HbA1c target than patients with a lower BMI [9]. Weight gain is also a known side effect of many oral antidiabetic drugs (OADs) and insulins used to treat T2DM, and may be associated with an increased risk of cardiovascular disease [10, 11]. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are a class of drugs that act by increasing glucose-dependent insulin secretion, preserving b-cell function, suppressing glucagon levels, and slowing gastric emptying [12, 13]. Unlike other therapies in T2DM, treatment with GLP-1 RA is typically associated with weight loss [14–17] and may also reduce cardiovascular risk [18]. In Japan, GLP-1 RAs are increasingly prescribed for the treatment of T2DM and several studies have demonstrated the efficacy and safety of GLP-1 RAs in the Japanese population [19–23]. Studies have also shown that GLP-1 RAs are more effective in Japanese/Asian populations when compared with European populations [24, 25], and are typically administered at a lower dose in the Japanese population [26]. This is because T2DM in Asian patients is primarily characterized by higher b-cell dysfunction, rather than insulin resistance [27], and GLP-1 RAs have a proven ability to improve b-cell function [28]. Therefore, GLP-1 RAs are a favorable choice of therapy for this population. Japanese patients with T2DM are also generally less obese than their European counterparts and the exposure of a fixed dose GLP-1 RA will be greater in lighter patients. Semaglutide once-weekly (QW) is a novel GLP-1 analogue administered at a 0.5 or 1.0 mg dose. The efficacy and safety of semaglutide QW has been assessed across the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program, which included two multicenter, head-to-head trials comparing semaglutide QW with exenatide QW or dulaglutide QW. In SUSTAIN 3, treatment with semaglutide QW provided significant reductions in HbA1c and weight when compared with exenatide QW, both as an addon to 1–2 OADs [metformin and/or sulfonylurea (SU) and thiazolidinedione (TZD)] [29]. In SUSTAIN 7, semaglutide QW also provided significant reductions in HbA1c and weight when compared with dulaglutide QW, both as an addon to metformin [30]; however, no Japanese patients were included in this trial. The efficacy and safety of semaglutide QW in a Japanese population with T2DM were demonstrated in (...truncated)