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

Amruta P. Patil, Prashant A. Shirure


Proton pump inhibitors (PPIs) block the parietal cell H+/K+ ATPase, are superior at suppressing acid secretion & promoting peptic ulcer healing, wildly used clinically for the therapy of gastro-esophageal reflex disease, gastritis due to excess stomach acid, and gastric ulcers. After blocking the production of gastric acid, the proton-pump inhibitors indirectly elevate serum gastrin levels via a negative feedback effect. Evidences are reported that gastrin promotes β cell neogenesis in pancreatic ductal complex, modest pancreatic β cell replication and improvement of glucose tolerance in animal models. Some recent clinical studies have shown improved glucose tolerance in type-2 diabetes mellitus (T2DM). Although PPIs may be possible candidates for a new approach in the therapy of diabetes, a prospective, long-term, randomized, double-blind, placebo-controlled study is needed to establish the effect of PPIs on glycemic control in a large number of patients with T2DM.


β cell neogenesis, Proton pump inhibitors, Raised gastrin level, Type 2 diabetes mellitus

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Tamaki M, Fujitani Y, Uchida T, Hirose T, Kawamori R, Watada H. Combination treatment of db/db mice with exendin‐4 and gastrin preserves β‐cell mass by stimulating β‐cell growth and differentiation. Journal of Diabetes Investigation. 2010 October;1(5):172-83.

Ashwini V, Suresha RN, Sushma VN, Pushpa VH, Yashoda C, Pragathi B. The Effect of Pantoprazole On Oral Glucose Induced Glycaemic Changes In Normal Albino Rats. International Journal of Pharma and Bio Science. 2012 July;3(3):516-25.

Najafipour F, Omidvar M, Reshadatjoo M. Effects of Pantoprazole on Serum Glucose Level in type two diabetic patients. International journal of current research and academic review. 2015 August;3(8):427-36.

Takebayashi K, Terasawa T, Naruse R, Hara K, Suetsugu M, Tsuchiya T, et al. Long Term Evaluation of Glycemic Control in Patients with Type 2 Diabetes Receiving Either Alogliptin and Lansoprazole or Alogliptin Mono-therapy for 3 Months Followed by Alogliptin Mono-therapy:A Retrospective Analysis. Dokkyo Journal of Medical Sciences. 2015;42(3):117-25.

Burkitt MD, Varro A, Pritchard DM. Importance of gastrin in the pathogenesis and treatment of gastric tumors. World J Gastroenterol. 2009;151-16.

Hansen OH, Pedersen T, Larsen JK, Rehfeld JF. Effect of gastrin on gastric mucosal proliferation in man. Gut. 1976;17:536-41.

Schubert ML, Makhlouf GM. Neural, hormonal, and paracrine regulation of gastrin and acid secretion. Yale J Biol Med. 1992;65:553-60.

Dufresne M, Seva C, Fourmy D. Cholecystokinin and gastrin receptors. Physiol Rev. 2006;86:805-47.

Bitziou E, Patel BA. Simultaneous detection of gastric acid and histamine release to unravel the regulation of acid secretion from the guinea pig stomach. Am J Physiol Gastrointest Liver Physiol. 2012;303:G396-403.

Saillan-Barreau C, Dufresne M, Clerc P, Sanchez D, Corominola H, Moriscot C, et al. Evidence for a functional role of the cholecystokinin-B/gastrin receptor in the human fetal and adult pancreas. Diabetes. 1999;48:2015-21.

Rooman I, Lardon J, Bouwens L. Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue. Diabetes. 2002;51:686-690.

Téllez N, Joa NNYG, Escoriza J, Vilaseca M, Montanya E. Gastrin treatment stimulates β-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats. Endocrinology 2011;152:2580-8.

Rehfeld JF, Stadil F. The effect of gastrin on basal-and glucose stimulated insulin secretion in man. J Clin Invest. 1973;52:1415-26.

Rickels M, Elahi D. Raising Serum Gastrin to Improve Glycemic Control in (Type 2) Diabetes: Another Limb of the Enteroinsular Axis? J Clin Endocrinol Metab. 2012;97(11):3915-6,

Zollinger RM, Ellison EH. Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg, 1955;142:709-28.

Meier JJ, Butler AE, Galasso R, Rizza RA, Butler PC. Increased islet -cell replication adjacent to intrapancreatic gastrinomas in humans. Diabetologia. 2006;49:2689-96.

Zhang JX, Ji MY, Song J, Lei HB, Qiu S, Wang J, et al. Proton pump inhibitor for non-erosive reflux disease: a meta-analysis. World J Gastroenterol. 2013;19:8408-19.

Bödvarsdóttir TB, Hove KD, Gotfredsen CF, Pridal L, Vaag A, Karlsen AE, et al. Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes. Diabetologia. 2010;53:2220-3.

Hove KD, Brøns C, Færch K, Lund SS, Petersen JS, Karlsen AE, et al. 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. Diabetologia. 2013;56:22-30.

Boj-Carceller D, Bocos-Terraz P, Moreno-Vernis M, Sanz-Paris A, Trincado-Aznar P, Albero-Gamboa R. Are proton pump inhibitors a new antidiabetic drug? A cross sectional study. World J Diabetes. 2011;2:217-20.

Barchetta I, Guglielmi C, Bertoccini L, Calella D, Manfrini S, Secchi C, et al. Therapy with proton pump inhibitors in patients with type 2 diabetes is independently associated with improved glycometabolic control. Acta Diabetol; 2015.

Crouch MA, Mefford IN, Wade EU. Proton pump inhibitor therapy associated with lower glycosylated hemoglobin levels in type 2 diabetes. J Am Board Fam Med. 2012;25:50-4.

Singh PK, Hota D, Dutta P, Sachdeva N, Chakrabarti A, Srinivasan A, et al. Pantoprazole improves glycemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2012;97:E2105-8.

Rau TT, Sonst A, Rogler A, Burnat G, Neumann H, Oeckl K, et al. Gastrin mediated down regulation of ghrelin and its pathophysiological role in atrophic gastritis. J Physiol Pharmacol. 2013;64:719-25.

Clerc P, Coll Constans MG, Lulka H, Broussaud S, Guigné C, Leung-Theung-Long S, et al. Involvement of cholecystokinin 2 receptor in food intake regulation: hyperphagia and increased fat deposition in cholecystokinin 2 receptor-deficient mice. Endocrinology. 2007;148:1039-49.

Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of Acid-Suppressive Drugs and Risk of Fracture: A Meta-analysis of Observational Studies. Annals of Family Medicine. 2011;9:257-67.

Lo WK, Chan WW. Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis. Clin Gastroenterol Hepatol. 2013;11:483-90.