Beneficial effects of SGLT2 inhibitor in diabetic patients with metabolic syndrome
Canagliflozin improves risk factors of metabolic syndrome in patients with type 2 diabetes mellitus and metabolic syndrome
Literature - Davies MJ, Merton KW, Vijapurkar U, et al. - Diabetes Metab Syndr Obes. 2017;10:47-55Background
Canagliflozin, an SGLT2 inhibitor, increases urinary glucose excretion leading to improved glycaemic control, body weight, and blood pressure in type 2 diabetes mellitus (T2DM) patients [1-4]. These improvements suggest that canagliflozin may be an effective treatment for improving the components of metabolic syndrome in T2DM patients, including dyslipidaemia, central obesity, hypertension and glucose intolerance.
In this post-hoc analysis, the effects of canagliflozin versus glimepiride (study 1, on a metformin background) and versus sitagliptin 100 mg (study 2, on a metformin and sulfonylurea background) were evaluated in patients with T2DM and metabolic syndrome [5,6].
Main results
- At week 52 in study 1, canagliflozin 100 mg was associated with similar reductions in HbA1c compared with glimepiride at week 52. Canagliflozin 300 mg was associated with greater reductions in HbA1c compared with glimepiride.
- Compared with glimepiride, canagliflozin 100 and 300 mg led to greater reductions in body weight, BMI, waist circumference, SBP and DBP.
- Canagliflozin 100 and 300 mg were associated with larger increases in HDL-C and LDL-C, as well as with numeric reductions in triglycerides versus glimepiride at 52 weeks.
- After 52 weeks, 87% of patients in the canagliflozin 100 mg group, 86% of patients in the canagliflozin 300 mg group, and 93% of patients in the glimepiride group met the criteria for metabolic syndrome diagnosis.
- At week 52 in study 2, canagliflozin 300 mg led to greater reductions in HbA1c and FPG versus sitagliptin 100 mg, as well as greater reductions in body weight, BMI, waist circumference, SBP and DBP.
- Increases in HDL-C and LDL-C and reductions in triglycerides were seen with canagliflozin 300 mg versus sitagliptin 100 mg.
- The proportion of patients who met the criteria for metabolic syndrome at 52 weeks was 89% in the canagliflozin 300 mg group and 95% in the sitagliptin 100 mg group.
- In the overall population of each study canagliflozin was generally well tolerated.
- In study 1, compared with glimepiride, canagliflozin 100 mg and 300 mg were associated with higher incidences of genital mycotic infections (male 1.1 vs 6.7 and 8.3% resp., female 2.3 vs. 11.3 and 13.9% resp.), urinary tract infections (4.6 vs 6.4 and 6.4% resp.) and osmotic diuresis–related AEs (1.7 vs. 5.6 and 6.2% resp.).
- The incidence of documented hypoglycaemia was significantly lower with canagliflozin 100 and 300 mg versus glimepiride (5.6 and 4.9 vs 34.2% resp.).
- In study 2, compared with sitagliptin 100 mg, canagliflozin 300 mg was associated with higher incidences of genital mycotic infections (male 9.2 vs 0.5%, female 15.3 vs 4.3%) and osmotic diuresis–related AEs (5.0 vs 2.4%) and the incidence of urinary tract infections was similar between groups (4.0 vs 5.6%).
- When added to a background of metformin and sulfonylurea, the incidence of documented hypoglycaemia was similar with canagliflozin 300 mg and sitagliptin 100 mg (43.2 vs 40.7%).
Conclusion
In a post-hoc analysis of two studies, canagliflozin had beneficial effects on body weight, BMI, waist circumference, SBP, DBP and HDL-C compared with glimepiride or sitagliptin in T2DM patients with metabolic syndrome. In the overall study populations, canagliflozin was generally well tolerated, with a higher incidence of genital mycotic infections and osmotic diuresis–related AEs.
References
1. Stenlöf K, Cefalu WT, Kim KA, et al. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATAM study. Curr Med Res Opin. 2014;30(2):163–175.
2. Lavalle-González FJ, Januszewicz A, Davidson J, 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(12):2582–2592.
3. Wilding JP, Charpentier G, Hollander P, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: a randomised trial. Int J Clin Pract. 2013;67(12):1267–1282.
4. Forst T, Guthrie R, Goldenberg R, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab. 2014;16(5):467–477.
5. Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013;382(9896):941–950.
6. Schernthaner G, Gross JL, Rosenstock J, 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(9):2508–2515.
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