Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes

Abstract

Aim:To compare the efficacy and safety of monotherapy with sitagliptin and metformin in treatment-naïve patients with type 2 diabetes. Methods: In a double-blind study, 1050 treatment-naïve patients (i.e. not taking an antihyperglycaemic agent for ≥16 weeks prior to study entry) with type 2 diabetes and an HbA 1c 6.5-9% were randomized (1:1) to treatment with once-daily sitagliptin 100 mg (N = 528) or twice-daily metformin 1000 mg (N = 522) for 24 weeks. Metformin was up-titrated from 500 to 2000 mg per day (or maximum tolerated daily dose ≥1000 mg) over a period of 5 weeks. The primary analysis used a per-protocol (PP) approach to assess whether sitagliptin was non-inferior to metformin based on HbA 1c change from baseline at week 24. Non-inferiority was to be declared if the upper boundary of the 95% confidence interval (CI) for the between-group difference in this endpoint was <0.40%. Results:From a mean baseline HbA 1c of 7.2% in the PP population, HbA 1c change from baseline was −0.43% with sitagliptin (n = 455) and −0.57% with metformin (n = 439). The between-group difference (95% CI) was 0.14% (0.06, 0.21), thus confirming non-inferiority. Baseline HbA 1c influenced treatment response, with larger reductions in HbA 1c observed in patients with baseline HbA 1c ≥8% in the sitagliptin (-1.13%; n = 74) and metformin (-1.24%; n = 73) groups. The proportions of patients at week 24 with HbA 1c values at the goals of <7 or <6.5% were 69 and 34% with sitagliptin and 76 and 39% with metformin, respectively. Fasting plasma glucose changes from baseline were −11.5 mg/dL (-0.6 mmol/l) and −19.4 mg/dl (-1.1 mmol/l) with sitagliptin and metformin, respectively (difference in LS mean change from baseline [95% CI] = 8.0 mg/dl [4.5, 11.4]). Both treatments led to similar improvements from baseline in measures of homeostasis model assessment-β cell function (HOMA-β) and insulin resistance (HOMA-IR). The incidence of hypoglycaemia was 1.7% with sitagliptin and 3.3% with metformin (p = 0.116). The incidence of gastrointestinal-related adverse experiences was substantially lower with sitagliptin (11.6%) compared with metformin (20.7%) (difference in incidence [95% CI] = −9.1% [−13.6, −4.7]), primarily because of significantly decreased incidences of diarrhoea (3.6 vs. 10.9%; p < 0.001) and nausea (1.1 vs. 3.1%; p = 0.032). Body weight was reduced from baseline with both sitagliptin (LS mean change [95% CI] = −0.6 kg [−0.9, −0.4]) and metformin (-1.9 kg [-2.2, −1.7]) (p < 0.001 for sitagliptin vs. metformin). Conclusions:In this 24-week monotherapy study, sitagliptin was non-inferior to metformin in improving HbA 1c in treatment-naïve patients with type 2 diabetes. Although both treatments were generally well tolerated, a lower incidence of gastrointestinal-related adverse experiences was observed with sitagliptin.

Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Naïve Type 2 Diabetes

“…The overall incidence of AEs was lower across groups in this study compared with previous studies (11-23); the reason for this observation, which has been seen with other AHAs (41,42), is not known but may be related to the characteristics of the study population. The pattern of specific AEs observed with CANA in this study was consistent with previous reports (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), with a higher incidence of AEs related to the mechanism of SGLT2 inhibition (e.g., genital mycotic infections, volume depletion-related AEs, osmotic diuresis-related AEs) observed in all CANA treatment arms versus MET.…”

Long-term efficacy of sitagliptin for the treatment of type 2 diabetic patients in Japan

“…After the stratification of patients into three groups according to the degree of HbA1c reduction, candidate factors were listed and evaluated in relation to the glucose-lowering effect of sitagliptin. Baseline factors such as age, gender, duration of diabetes, BMI, co-prescribed OHA and the score for life-style assessment did not show significant relations to the reduction of HbA1c during 3 months of sitagliptin treatment, except for the baseline HbA1c level which was strongly correlated to it as previously reported [7,13]. In contrast, the reduction of PPG after one month could be a predictor for the forthcoming efficacy of sitaglitin because of its strong correlation to HbA1c reduction even after 3 months.…”

Efficacy and Safety of Dulaglutide Monotherapy Versus Metformin in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-3)

“…It is noteworthy to observe that in AWARD-3, the magnitude of HbA 1c change associated with both dulaglutide and metformin was smaller than generally reported in other monotherapy trials with the same compounds or other compounds of the GLP-1 receptor agonists class (10,(19)(20)(21)(22). The low mean HbA 1c at randomization (7.6% [60 mmol/mol]) in AWARD-3 was a likely contributor to this observation, as it is well established that interventioninduced HbA 1c changes are confounded by baseline glycemic status (23,24 HbA 1c targets with dulaglutide in AWARD-3 was comparable to that observed in both of these two studies.…”