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ObjectiveTo compare the efficacy and safety of dapagliflozin and dapagliflozin plus saxagliptin vs glimepiride as add‐on to metformin in patients with type 2 diabetes.Research design and methodsThis 52‐week, multicentre, double‐blind, active‐controlled study (NCT02471404) randomized (1:1:1) patients (n = 939; HbA1c 7.5%‐10.5%) on metformin monotherapy (≥1500 mg/day) to add‐on dapagliflozin 10 mg, dapagliflozin 10 mg plus saxagliptin 5 mg, or glimepiride 1 to 6 mg (titrated). The primary efficacy end point was change in HbA1c from baseline to Week 52.ResultsBaseline mean age, diabetes duration and HbA1c were 58.4 years, 7.0 years and 8.3%, respectively. Adjusted mean HbA1c change from baseline was −1.20% with dapagliflozin plus saxagliptin and −0.82% with dapagliflozin, vs −0.99% with glimepiride (mean dose at Week 52, 4.6 mg). Changes in body weight (−3.2 kg and −3.5 kg vs +1.8 kg) and systolic blood pressure (SBP; −6.4 mm Hg and −5.6 mm Hg vs −1.6 mm Hg) were significantly greater with dapagliflozin plus saxagliptin and dapagliflozin than with glimepiride. FPG decreased significantly with dapagliflozin plus saxagliptin compared with glimepiride (−2.1 mmol/L vs −1.5 mmol/L) and was similar with dapagliflozin (−1.6 mmol/L) compared with glimepiride. Confirmed incidence of hypoglycaemia was lower with dapagliflozin regimens than with glimepiride (0 and 1 vs 13 patients) and fewer patients required rescue. Genital infections were more frequent with dapagliflozin; other AE profiles were similar.ConclusionsDapagliflozin, saxagliptin and metformin improved glycaemic control compared with glimepiride plus metformin; add‐on of dapagliflozin alone showed efficacy similar to that of glimepiride. Both dapagliflozin regimens decreased body weight and SBP, with a lower incidence of hypoglycaemia compared with glimepiride.

Statins are currently the most effective drugs in reducing low-density lipoprotein cholesterol (LDL-C). With their mechanism of action, by inhibiting 3-hydroxy-3 methylglutharyl coenzyme A reductase, statins decrease cholesterol production. The same biosynthetic pathway is shared by ubiquinone or coenzyme Q10. Statins block production of dekaprenyl-4-benzoate, a precursor of coenzyme Q10 (CoQ10), which is an essential component in mitochondrial transport system. Ubiquinone deficiency may affect oxidative phosphorylation and adenosine triphosphate production, which can subsequently result in impairing of muscle energy metabolism and contribute to development of myopathy. Statin therapy also decreases antioxidant status in the body, resulting in to increase in free radical damage to cells in various parts of body; liver, nerves, muscles. Statins can decrease natural antioxidant protection present in our body and predispose toxicity. Statin-associated myopathy is the most common side effect of statin treatment often lead to statin dose reduction, or therapy cessation, which can negatively affect cardiovascular risk management. The spectrum of statin-related myopathy ranges from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. Observational studies suggest that myalgia can occur in up to 10% of persons prescribed statins, whereas rhabdomyolysis continues to be rare. Statins lower circulating levels of CoQ10 up to 54%, whereas several studies did not confirmed a lowering of CoQ10 levels in muscles during statin therapy and the evidence was given also on low dose of statin therapy, which did not appear to reduce intramuscular levels of CoQ10 in symptomatic patients with statin myopathy. The conflicting results have been published on the impaired mitochondrial function, which was found during the analysis of the myocyte cells in patients treated with statins. The supplementation of CoQ10 results in increasing of serum CoQ10, but it is not clear if it relieves myopatic symptoms in statin treated patients. Yet available intervention studies reported contrasting results and just two of them proved benefit of CoQ10 supplementation. Hence coenzyme Q10 supplementation is not currently recommended for routine use in the prophylaxis of statin toxicity.