Effects of 12 weeks’ treatment with a proton pump inhibitor on insulin secretion, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind prospective placebo-controlled study

Abstract

Aims/hypothesis Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised doubleblind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA 1c and cardiovascular risk factors in type 2 diabetes. Methods Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n020) or placebo (n021) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA 1c and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements. Results Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049±17,659 vs 27,270±32,004 pmol/l × min (p=0.838). In the placebo group AUC for insulin decreased from 27,392±14,348 pmol/l × min to 22,938± 11,936 pmol/l × min (p=0.002). Esomeprazole treatment (n020) caused a ninefold increase in the AUC for gastrin. HbA 1c increased from 7.0±0.6% (53±5 mmol/mol) to 7.3±0.8% (56 ±6 mmol/mol) in the esomeprazole-treated group and from 7.0 ±0.6% (53±5 mmol/mol) to 7.4±0.8% (57±6 mmol/mol) in the placebo group (n021) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p>0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p<0.05). No change in BP was seen in the patients treated with esomeprazole. Conclusions/interpretation Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.Trial registration ClinicalTrials.gov NCT00699426

Effects of 12 weeks of treatment with fermented milk on blood pressure, glucose metabolism and markers of cardiovascular risk in patients with type 2 diabetes: a randomised double-blind placebo-controlled study

“…The primary endpoint of the combined 2!2 factorial study of the effects of esomeprazole and fermented milk on cardiometabolic risk factors in T2D patients was change in insulin secretion as explained previously (12). We had an 80% power to detect a 25% change in this outcome.…”

“…All analyses studying the effect of Cardi04 yogurt treatment were performed with and without adjustment for the esomeprazole intervention. Sample size calculation was based on the esomeprazole treatment as previously described (12).…”

“…The study was performed at the Steno Diabetes Center A/S, Denmark, during the period from 2008 to 2009. The esomeprazole treatment results of the 41 T2D patients included in this factorial study have been published elsewhere (12).…”

“…The patients were concurrently randomly assigned to receive either esomeprazole 40 mg or matching placebo with a 2!2 factorial design as previously described (12). The allocation sequence was concealed in sealed envelopes and locked away from the researcher enrolling and assessing participants.…”

Effect of add-on proton pump inhibitors on parameters of glycemic control in type-2 diabetic patients

“…19 Therefore, these agents appear to have the possibility of being a new approach for the therapy of diabetes. [20][21][22][23] Thus, the hypothesis that proton pump inhibitors can be used to treat type 2 diabetes.…”