Factors Influencing Changes in Hemoglobin A1c and Body Weight During Treatment of Type 2 Diabetes With Ipragliflozin: Interim Analysis of the ASSIGN-K Study

Self Cite

In the present randomized study, we assessed the efficacy of ipragliflozin compared with sitagliptin in 124 Japanese patients with type 2 diabetes. Sodium-glucose co-transporter-2 inhibitor-naïve and incretin-related agent-naïve patients were randomly assigned to receive additional 50 mg ipragliflozin or sitagliptin. The primary endpoint was the proportion of participants with >0.5% decrease in glycated haemoglobin (HbA1c) without body weight gain at 12 weeks. For secondary endpoints, we measured several biomarkers related to metabolic changes. After 12 weeks, 53.9% of participants in the ipragliflozin and 42.9% in the sitagliptin group reached the primary endpoint (P = 0.32). Decreases in homeostatic model assessment of insulin resistance, body fat percentage and skeletal muscle mass index, and increases in free fatty acids, ketone body concentration and HDL cholesterol levels were greater in the ipragliflozin group. Increases in homeostatic model assessment of β-cell function and decreases in proinsulin-to-insulin ratio were greater in the sitagliptin group. No serious adverse events occurred in either group. In conclusion, ipragliflozin had beneficial effects on fat reduction, insulin resistance and lipid metabolism, while sitagliptin had beneficial effects on β-cell function.

Section: Discussioncontrasting

confidence: 77%

“…9,10 The absolute reduction in HbA1c by antidiabetic agents, including ipragliflozin and sitagliptin, has been shown to be lower in patients who have relatively low baseline HbA1c levels. 11,12 The proportion of participants with a decrease in HbA1c levels of ≥0.5%…”

Section: Discussionmentioning

confidence: 99%

Comparative study of the effects of ipragliflozin and sitagliptin on multiple metabolic variables in Japanese patients with type 2 diabetes: A multicentre, randomized, prospective, open‐label, active‐controlled study

Tsurutani

Nakai

Inoue

et al. 2018

Self Cite

“…Greater weight loss was associated with several patient characteristics, including absence of a history of heart failure or hypertension, use of insulin, use of GLP-1 agonist and non-use of a sulphonylurea, but the mechanism for the greater percentage reduction in weight loss in these patients was not apparent. Similarly unclear was the reason why weight reductions in this study and a previous report 30 were greater among those with lower baseline HbA1c levels at 3 months-the opposite might have been anticipated, as renal excretion of glucose and calories with SGLT2 inhibition would be lower among those with well-controlled glycaemia. 31 The observed differences in weight reduction between eGFR subgroups were not linearly associated with renal function as might have been expected.…”

Section: Discussioncontrasting

confidence: 53%

Clinical outcomes with canagliflozin according to baseline body mass index: results from post hoc analyses of the CANVAS Program

Ohkuma

Gaal

Shaw

et al. 2020

Aims Sodium glucose co‐transporter 2 (SGLT2) inhibitors reduce several cardiovascular risk factors, including plasma glucose, blood pressure, albuminuria and body weight. Long‐term treatment lowers risks of cardiovascular and renal events. The objective of this post hoc analysis was to determine the effects of canagliflozin treatment versus placebo on clinical outcomes in relation to body mass index (BMI). Materials and methods The CANVAS Program randomized 10 142 participants with type 2 diabetes to canagliflozin or placebo. These analyses tested the consistency of canagliflozin treatment effects across BMI levels for cardiovascular, renal, safety and body weight outcomes in three groups defined by baseline BMI: <25, 25‐<30 and ≥30 kg/m2. Results In total, 10 128 participants with baseline BMI measurements were included. There were 966 participants with BMI <25 kg/m2, 3153 with BMI 25‐<30 kg/m2 and 6009 with BMI ≥30 kg/m2. Mean percent body weight reduction with canagliflozin compared with placebo was greater at 12 months [−2.77% (95% confidence interval (CI): −2.95, ‐2.59)] than at 3 months [‐1.72% (95% CI: ‐1.83, ‐1.62)]. The hazard ratios (HRs) for canagliflozin compared with placebo control for the composite outcome of cardiovascular death, non‐fatal myocardial infarction or non‐fatal stroke were 1.03 (95% CI: 0.66, 1.59) in participants with BMI <25 kg/m2, 0.97 (0.76, 1.23) with BMI 25‐<30 kg/m2 and 0.79 (0.67, 0.93) with BMI ≥30 kg/m2 (P for heterogeneity = 0.55). The effects of canagliflozin on each component of the composite were also similar across BMI subgroups, as were effects on heart failure and renal outcomes (P for heterogeneity ≥0.19). The effects on safety outcomes were also broadly similar. Conclusions Canagliflozin improved cardiovascular and renal outcomes consistently across patients with a broad range of BMI levels.

“…A pooled analysis of the effect of dapagliflozin on cardiovascular risk factors according to eGFR confirmed the decreased efficacy in reducing HbA1c among patients with eGFR ≥45 to <60 mL/min/1.73 m 2 compared with those with eGFR ≥60 to <90 or ≥ 90 mL/min/1.73 m 2 (interaction P < .001), with no influence on the effect of treatment on body weight . Finally, an interim analysis of the ASSIGN‐K study showed no relationship between sex and weight loss in Japanese patients with T2DM …”

Section: Discussionmentioning

confidence: 86%

Effects of exenatide once weekly plus dapagliflozin, exenatide once weekly alone, or dapagliflozin alone added to metformin monotherapy in subgroups of patients with type 2 diabetes in the DURATION‐8 randomized controlled trial

Frías

Hardy

Ahmed³

et al. 2018

This analysis assessed whether responses with exenatide once weekly plus dapagliflozin (n = 231), exenatide once weekly alone (n = 230), or dapagliflozin alone (n = 233) differed in key patient subpopulations of the DURATION‐8 trial. Potential treatment‐by‐subgroup interactions for changes in glycated haemoglobin (HbA1c) and body weight after 28 weeks were evaluated among subgroups determined by baseline HbA1c, age, sex, body mass index, type 2 diabetes duration, race, ethnicity and estimated glomerular filtration rate (eGFR). Exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all subgroups: least‐squares mean reductions ranged from −8.4 to −26.1 mmol/mol (−0.77% to −2.39%) for HbA1c and from −2.07 to −4.55 kg for body weight. Potential treatment‐by‐subgroup interactions (P < .10) were found for HbA1c change by age (P = .016) and eGFR (P = .097). Age subgroup analysis findings were not consistent with expected mechanistic effects, with the small number of patients aged ≥65 years (n = 74 vs n = 499 for patients aged <65 years) limiting the interpretability of the interaction term. In the exenatide once weekly plus dapagliflozin and dapagliflozin groups, but not the exenatide once weekly group, HbA1c reductions were greater among patients with eGFR ≥90 vs ≥60 to <90 mL/min/1.73 m2 (least‐squares mean reductions of −23.6 vs −19.0 mmol/mol [−2.16% vs −1.74%], −17.3 vs −12.0 mmol/mol [−1.58% vs −1.10%], and −17.7 vs −16.9 mmol/mol [−1.62% vs −1.55%] for the respective treatments); this was consistent with the mechanism of action of dapagliflozin. A potential treatment‐by‐subgroup interaction was observed for change in body weight by sex (P = .099), with greater weight loss for women vs men across all treatments (range −2.56 to −3.98 kg vs −0.56 to −2.99 kg). In conclusion, treatment with exenatide once weekly plus dapagliflozin reduced HbA1c and body weight across all patient subgroups and was more effective than exenatide once weekly or dapagliflozin alone in all adequately sized subgroups.