Tolerability of canagliflozin in patients with type 2 diabetes mellitus fasting during Ramadan: Results of the Canagliflozin in Ramadan Tolerance Observational Study (CRATOS).

AIMS: There is a large population of people with type 2 diabetes mellitus (T2DM) who are Muslim and fast during Ramadan. Changes in the pattern and amount of meal and fluid intake during Ramadan, in addition to the long fasting hours, may increase the risk of hypoglycaemia, hyperglycaemia, and dehydration. The Canagliflozin in Ramadan Tolerance Observational Study (CRATOS) evaluated the tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with sulphonylureas among patients with T2DM who fast during Ramadan. METHODS: This non-randomised, parallel-cohort, prospective, comparative, observational study was conducted in the Middle East during Ramadan and enrolled patients who were taking canagliflozin (n=162) or any sulphonylurea (n=159) added to metformin±dipeptidyl peptidase-4 inhibitor. The proportion of patients who experienced hypoglycaemia events was assessed as the primary end-point. Between-cohort comparisons were adjusted using propensity score analysis. RESULTS: During Ramadan, fewer patients experienced symptomatic hypoglycaemia with canagliflozin vs sulphonylurea (adjusted odds ratio: 0.273 [95% CI: 0.104, 0.719]). Of hypoglycaemia events for which blood glucose was measured, two of six with canagliflozin and 27 of 37 with sulphonylurea were confirmed by blood glucose <3.9 mmol/L. More patients treated with canagliflozin experienced volume depletion events compared with sulphonylurea (adjusted odds ratio: 3.5 [95% CI: 1.3, 9.2]). Missed fasting days were few and medication adherence was high in both groups. No patients treated with canagliflozin and 9.4% treated with sulphonylurea adjusted their medication dose near the beginning of Ramadan. Both treatments were generally well tolerated, with low rates of adverse events and no serious adverse events in either group. CONCLUSIONS: Overall, these findings support the use of canagliflozin for the treatment of adults with T2DM who fast during Ramadan. CLINICALTRIALS. GOV IDENTIFIER: NCT02737657.

Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates.

AIMS: Patients with type 2 diabetes mellitus (T2DM) have increased risk of adverse events (AEs; e.g. dehydration, hypoglycaemia) in hot weather. This analysis assessed the efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in patients with T2DM who live in hot climates. METHODS: This post hoc analysis evaluated patients with T2DM using pooled data from four 26-week, placebo-controlled studies (N=2,313) and data from a 104-week, active-controlled study (add-on to metformin vs glimepiride; N=1,450). Changes in HbA1c, fasting plasma glucose (FPG), body weight and blood pressure (BP) were assessed in subsets of patients living in hot climates (pooled, placebo-controlled studies, n=611; active-controlled study, n=307) and those living in other climates (i.e. other climate subset; pooled, placebo-controlled studies, n=1,702; active-controlled study, n=1,143). Safety was assessed based on AE reports. RESULTS: Canagliflozin 100 and 300 mg lowered HbA1c, FPG, body weight and BP vs placebo over 26 weeks and glimepiride over 104 weeks in the hot climate subsets. Canagliflozin was generally well tolerated in the hot climate subsets, with a higher incidence of AEs related to the mechanism of SGLT2 inhibition (i.e. genital mycotic infections). Volume depletion-related AEs were low across groups. CONCLUSION: Canagliflozin improved glycaemic control, lowered body weight and BP, and was generally well tolerated in patients with T2DM living in hot climates compared with placebo over 26 weeks or glimepiride over 104 weeks. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01081834, NCT01106677, NCT01106625, NCT01106690, NCT00968812.