Effect of proton pump inhibitors on glycemic control in patients with diabetes

Table 1 Studies showing glucose-lowering effect of proton pump inhibitors in patients with type 2 diabetes

Mefford et al[26]	Outcome measures: HbA1c levels in patients with type 2 diabetes taking PPIs (n = 65) vs those not taking PPIs (n = 282) was evaluated in cross-sectional design
	Key findings: There was a significant difference in HbA1c in patients taking PPIs vs those not taking PPIs (7.0% vs 7.6%, P = 0.002)
	Safety information: No information is described
Boj-Carceller et al[27]	Outcome measures: HbA1c levels in patients with type 2 diabetes taking PPIs (n = 54) vs those not taking PPIs (n = 43) was evaluated in cross-sectional design
	Key findings: HbA1c was significantly lower in type 2 diabetic patients who take PPIs compared with those not taking PPIs (6.7% ± 1.0% vs 7.3% ± 1.4%, P = 0.018) Safety information: No information is described
Barchetta et al[28]	Outcome measures: HbA1c and FPG levels in patients with type 2 diabetes taking PPIs for longer than 2 yr (n = 245) vs those not taking PPIs (n = 303) was evaluated in cross-sectional design
	Key findings: Patients with PPIs had significantly lower HbA1c (7.1% ± 1.07% vs 7.4% ± 1.4%, P = 0.011) and FPG (127 ± 36.9 mg/dL vs 147.6 ± 49.6 mg/dL, P < 0.001) levels than those who did not take PPIs
	Safety information: No information is described
Hove et al[29]	Outcome measures: HbA1c levels were retrospectively evaluated in patients with type 2 diabetes. Patients were assigned to 2 groups: 21 patients who had taken esomeprazole (a PPI) for 11.3 ± 3 mo and 21 control subjects
	Key findings: There was a tendency for a decline in HbA1c in the patients treated with this PPI (8.6% to 7.9%, P = 0.054). In a subgroup with HbA1c > 9% (n = 11), the reduction was statistically significant (9.7% to 8.5%, P = 0.004). No change in HbA1c was observed in the control group (9.2% to 9.9%, P = 0.455)
	Safety information: No information is described
Han et al[24]	Outcome measures: HbA1c was retrospectively evaluated in type 2 diabetic patients treated with PPIs for ≥ 2 mo (mean duration: 180 d, n = 43)
	Key findings: There was no significant change in HbA1c levels (6.86% ± 1.10% to 6.77% ± 1.07%; P = 0.406)
	Safety information: No information is described
Crouch et al[30]	Outcome measures: 71 individuals with type 2 diabetes who were not taking insulin was retrospectively investigated for the change of HbA1c
	Key findings: The mean HbA1c was 7.11% during periods with either prescription or over-the-counter PPIs, vs 7.7% during periods without PPIs (a significant difference; P = 0.001)
	Safety information: No information is described
Singh et al[31]	Outcome measures: The effect of a 12-wk pantoprazole (40 mg twice daily) therapy regimen on HbA1c, FPG, serum insulin, serum gastrin levels was prospectively measured in patients with type 2 diabetes in randomized double-blind, placebo-controlled study design. Thirty one eligible patients were randomly assigned to receive either pantoprazole (n = 16) or placebo (n = 15)
	Key findings: HbA1c and FPG significantly decreased with pantoprazole therapy (7.60% ± 1.17% to 6.80% ± 1.16%, P < 0.001 for HbA1c and 126.3 ± 10.3 to 109.2 ± 13.0 mg/dL, P = 0.017 for FPG), and the differences were significant between the two groups (P = 0.004 for HbA1c, P = 0.019 for FPG). Pantoprazole significantly increased both plasma gastrin (P < 0.001) and insulin levels (P < 0.001)
	Safety information: Nine patients reported adverse events as nausea, vomiting, headache and myalgia, which were similar and mild in the both groups. None of the patients had hypoglycemia
González-Oritz et al[32]	Outcome measures: The effect of pantoprazole (40 mg once daily for 45 d) on insulin secretion in 14 drug naive patients with type 2 diabetes was prospectively investigated in a randomized, double-blind, placebo-controlled study design. Insulin secretion evaluated by hyperglycemic and hyperinsulinemic clamp technique, HbA1c, FPG and serum lipids were measured
	Key findings: Significant increases in total insulin secretion (P = 0.028), and significant decreases in HbA1c levels (7.5% to 6.6%; P = 0.018) but not FPG levels (P = 0.236) were found with pantoprazole therapy (n = 7), while there was no significant changes in these parameters in patients treated with placebo (n = 7). There were no significant changes in serum lipids in both groups Safety information: Two patients had mild headache (one in each group)
Hove et al[25]	Outcome measures: The effect of esomeprazole on glycemic control in 41 type 2 diabetic patients using either dietary control or therapy by anti-diabetic agents was prospectively examined in a randomized double-blind placebo-controlled 2 × 2 factorial study. These patients were randomly assigned to receive either add-on esomeprazole (40 mg daily, n = 20) or placebo (n = 21) for 12 wk. Insulin secretion, HbA1c levels and cardiovascular risk factors were evaluated Key findings: In the esomeprazole-treated group, the AUC (area under the curve) for insulin did not change (P = 0.838), while the AUC for the placebo group significantly decreased (P = 0.002). HbA1c increased from 7.0% ± 0.6% to 7.3% ± 0.8% (P < 0.05) in the esomeprazole-treated group and from 7.0% ± 0.6% to 7.4% ± 0.8% (P < 0.05) in the placebo group (no significant difference in change between both treatments; unadjusted, P = 0.297). The differences in cardiovascular risk factors were not significant between the two groups
	Safety information: Flatulence in 2 patients and diarrhea in 1 patient was reported in lansoprazole group, and flatulence in 2 patients and intermittent diarrhea in 1 patient was reported in placebo group
Takebayashi et al[72]	Outcome measures: The effect of alogliptin and lansoprazole (n = 46) combination therapy compared with alogliptin therapy without lansoprazole (n = 43) on glycemic control was investigated in a randomized open-label study. After 3 mo of treatment, the changes in HbA1c, FPG, serum gastrin were evaluated
	Key findings: A significant decrease in both HbA1c and FPG (respective 7.6% ± 0.6% to 6.8% ± 0.7%, P < 0.0001, 52.0 ± 35.6 to 127.3 ± 27.4 mg/dL, P < 0.0001 in the combination therapy group, and respective 7.7% ± 0.5% to 6.7% ± 0.5%, P < 0.0001, 153.6 ± 34.4 to 128.5 ± 26.6 mg/dL, P = 0.0001 in the alogliptin therapy group) was obtained. There were no significant differences in changes in HbA1c, FPG (P = 0.2945, P = 0.1901, respectively) and significant elevation in change in gastrin (approximate twofold, P = 0.0004) before and after therapy between the combination and the alogliptin mono therapy group
	Safety information: In alogliptin group, 1 patient discontinued the drug due to epi-gastric pain. In the combination group, 1 patient withdrew due to a mild cerebral infarction, and 1 patient noticed occasional hypoglycemic symptoms

PPIs: Proton pump inhibitors.