SummaryAimsThere 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.MethodsThis 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.ResultsDuring 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.ConclusionsOverall, these findings support the use of canagliflozin for the treatment of adults with T2DM who fast during Ramadan.ClinicalTrials.gov Identifier: NCT02737657

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In the present study, the actions of several compounds with different intrinsic activities and BDZ receptor selectivity were examined in two well established animal models of anxiety: the open field test (OFT) and Vogel's punished drinking text (VT). Full agonists at the BDZ GABAA receptor (midazolam and diazepam) showed anxiolytic-like effects in both tests; however, the doses necessary to disinhibit animal behavior controlled by fear were higher in the VT than in the OFT. None of the partial BDZ receptor agonists studied (bretazenil, Ro 19-8022 and abecarnil) diminished neophobia-like behavior of rats in the OFT, and their sedative influence on gross behavior prevailed. On the other hand, all three drugs produced a clear-cut anxiolytic effect in the VT. A selective BDZ, receptor subtype full agonist (zolpidem) had a similar profile of action to that of partial agonists with an even stronger sedative effect in the OFT. Alpidem (a selective BDZ1 receptor partial agonist) did not reveal any anxiolytic action in either test. Flumazenil (an antagonist at the BDZ-GABAA receptors) also produced no effect in the OFT, or the VT. An inverse BDZ receptor agonist, beta-carboline-3-carboxylate methyl ester (beta-CCM), evoked an anxiogenic-like response in the OFT, but not in the VT. In summary, it appeared that partial agonists and selective ligands at BDZ1 receptors revealed less advantageous anxiolytic-like action than did full allosteric GABAA receptor modulators. This study also indicates the test dependent profiles of action of BDZ-GABAA receptor ligands. It also indirectly suggests a different neurobiological background underlying the applied tests.