The following article is part of our coverage of the Endocrine Society’s annual meeting (ENDO 2021) that is being held virtually from March 20-23, 2021. Endocrinology Advisor‘s staff will report on the top research in hormone science and clinical care. Check back for the latest news from ENDO 2021.


Treatment with a proton pump inhibitor (PPI) does not appear to be associated with improved glycemic control in patients with type-2 diabetes mellitus (T2DM), according to a new retrospective study presented at ENDO 2021, the Endocrine Society’s annual meeting. However, investigators found that C-peptide levels were significantly higher in patients with T2DM who were on PPI therapy suggesting higher insulin secretion.

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Vipin Verma, MD, et al. compared HbA1c, C‐peptide, and glucose levels in patients with and without active PPI therapy by reviewing the charts of patients with T2DM at least 18 years of age who received care between Jan. 1, 2018 and Dec. 31, 2018. A total of 215 patients met the study criteria and 71 patients were being treating with a PPI.  The researchers conducted a statistical analysis by using SPSS version 20.0 (SPSS, Armonk, NY: IBM Corp), and all values were presented as means ± SD. For this investigation, a p value of < 0.05 was considered to be significant. The team also performed independent T-test and chi-square test to compare parameters between the two groups.

The authors note that gastrin release from G cells stimulates cholecystokinin (CCK2) receptors throughout the body. While this mainly promotes gastric acid secretion, gastrin also stimulates CCK2 receptors located elsewhere, including the islet of the pancreas. Although gastrin increases insulin secretion and promotes pancreatic β cell neogenesis and replication, there is not a great deal known about the effect of PPIs on insulin-glucose homeostasis (c-peptide, HbA1c, and glucose) in patients with T2DM.

Treatment with a proton pump inhibitor decreases the pH of the stomach and stimulates gastrin secretion which could potentially indirectly promote insulin secretion and improve hemoglobin HbA1c. In the current investigation, there was no statistical differences regarding age, sex, race and BMI between the PPI group and non-PPI group. The same was true for HbA1c levels between the PPI group and non‐PPI group (8.6% ± 2.1 vs 8.3% ± 2.0, p value = 0.37).

The researchers found a significant increase in C‐peptide levels in the PPI group compared to non-PPI group (3.1 ng/mL ± 2.4 vs 2.4 ng/mL ± 2.3; p value = 0.037). The study also showed decreases in LDL cholesterol levels in the PPI group compared to non-PPI group (79.6 mg/dL ± 34.0 vs 89.73 mg/dL ± 32.9; p value = 0.046). However, there was a significantly greater incidence of coronary artery disease in the PPI group compared to the non-PPI group (p = 0.01).

The study showed that in patients with T2DM treatment with a PPI was not associated with improved glycemic control, but C-peptide levels were significantly higher in these patients compared to those not receiving a PPI suggesting higher insulin secretion. “The lack of difference in HbA1c levels may be a result of aggressive diabetic management by treating clinicians to achieve similar goal HbA1c in both groups,” authors wrote. More research is warranted to better understand the gastrin pathway and its potential for improving glycemic control, they wrote.

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Verma V, Cromer M, Riddick B, et al. The Effect of Proton Pump Inhibitors on Insulin-Glucose Homeostasis in Patients With Type 2 Diabetes Mellitus. Presented at ENDO 2021, the Endocrine Society’s annual meeting; March 20-23, 2021.