HbA1c and Weight: Canaglioflozin vs Sitaglitpin

The SGLT2 inhibitor canagliflozin decreases HbA1c and weight over 52 weeks more than the DPP-4 inhibitor sitagliptin, according to a study published in Postgraduate Medicine.¹

“The improvements in glycemic control and reductions in body weight provided by canagliflozin make it a promising treatment option for the majority of patients with T2DM who are obese or overweight, particularly since many other available treatments are generally considered weight neutral (e.g. metformin and DPP-4 inhibitors) or have been shown to contribute to weight gain (e.g. insulin, sulfonylureas, and thiazolidinediones),” wrote first author Guntram Schernthaner, MD, of Rudolfstiftung Hospital-Vienna, Vienna, Austria, and colleagues at Janssen Research & Development, LLC, (Raritan, NJ).

While weight loss may improve glycemic control and cardiovascular risk factors in T2DM, many patients are unable to achieve and maintain weight loss targets using recommended lifestyle modification alone. Less than adequate self-management and stage of diabetes progression may contribute. Anti-diabetes medications that target both HbA1c and weight loss might be attractive to such patients, according to the authors.

The post hoc analysis pooled data from two randomized controlled phase 3 studies. The first study compared canagliflozin 100 and 300 mg to sitagliptin 100 mg as adjunctive treatment to metformin.² The second compared canagliflozin 300 mg to sitagliptin 100 mg as adjunctive treatment to metformin plus a sulfonylurea. The pooled analysis included data from 1856 participants, with a mean baseline HbA1c of 8.0%, and a mean baseline body weight of 87.7 kg.

The study evaluated two composite endpoints: 1) decrease from baseline HbA1c and body weight; 2) achieving ADA and European Association for the Study of Diabetes recommended targets of HbA1c <7.0% and ≥5% decrease in body weight.

Key results:

• Decrease from baseline in HbA1c and body weight:

♦ Canagliflozin 100 mg: 67.7%

♦ Canagliflozin 300 mg: 72.6%

♦ Sitaglitpin 100 mg: 44.1%

♦ Compared to sitaglitpin, canagliflozin 100 mg was over twice as likely (OR 2.2 [1.7–2.9]), and canagliflozin 300 mg was over three times as likely (OR 3.4 [2.8–4.3]) to reach this endpoint

• Combined endpoint of HbA1c <7.0% and body weight reduction ≥5%

♦ Canagliflozin 100 mg: 18.9%

♦ Canagliflozin 300 mg: 18.3%

♦ Sitaglitpin 100 mg: 5.7%

♦ Compared to sitagliptin, canagliflozin 100 mg was almost three times as likely (ORs 2.9 [1.9–4.4]) and canagliflozin 300 mg was almost four times as likely (3.9 [2.7–5.6]) to reach this endpoint

• Adverse events (AEs):

♦ Similar overall incidence of AEs leading to study discontinuation, serious AEs, and volume depletion-related AEs for canagliflozin 100, canagliflozin 300 mg and sitagliptin 100 mg

♦ Higher incidence of genital mycotic infections (mostly mild to moderate), and osmotic diuresis adverse events (most mild) with canagliflozin

• Hypoglycemia with add-on to metformin:²

♦ Canagliflozin 100 mg: 6.8%

♦ Canagliflozin 300 mg: 6.8%

♦ Sitagliptin 100 mg: 4.1%

• Hypoglycemia with add-on to metformin plus a sulfonyurea:³

♦ Canagliflozin 300 mg: 43.2%

♦ Sitagliptin 100 mg: 40.7%

♦ Similar incidence of severe hypoglycemia with canagliflozin 300 mg (4.0%) and sitagliptin 100 mg (3.4%)

The authors pointed out that the post hoc nature of the study precluded analysis for statistical significance. They noted that longer-term studies are needed that can compare how well canagliflozin lowers HbA1c and body weight to active comparators, or in addition to intensive lifestyle modification.

“Taken together, the results of this study and those from previous reports suggest that the improvement in glycemic control provided by canagliflozin, with the added benefit of weight reduction, make it an effective treatment option compared with sitagliptin for patients with T2DM,” they concluded. 

Take-home Points

• Post-hoc analysis of two phase 3 randomized controlled trials found that canagliflozin lowers HbA1c and body weight over 52 weeks more than sitagliptin.

• Results showed similar overall incidence of adverse events (AEs) leading to study discontinuation, serious AEs, and volume depletion-related AEs for canagliflozin and sitagliptin; and higher incidence of genital mycotic infections and osmotic diuresis adverse events with canagliflozin

• Hypoglycemia events were higher with canagliflozin 300 mg added to metformin and a sulfonylurea, compared to sitaglitpin 100 mg.

The study was sponsored by Janssen Research & Development. Drs Vijapurkar, Qiu, and Canovatchel are full-time employees of Janssen Research & Development, LLC. One or more authors reports serving on advisory boards, speaking for, speaker bureau participation, research support, consulting XXX for one or more of the following:  Eli Lilly, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda,  Johnson & Johnson, Sanofi, Merck, Novo Nordisk, Merck Sharp & Dohme, Janssen-Cilag, GlaxoSmithKline, Merck Serono, Silanes, Novartis, Pfizer, Amgen, Aspire Bariatrics.

References:

1. Schernthaner G, et al. Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes. Postgrad Med. 2016 Jul 26:1-6.

2. Lavalle-González FJ, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia. 2013;56:2582-2592.

3. Schernthaner G, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week, randomized trial. Diabetes Care. 2013;36:2508-2515.