Proton Pump Inhibitor Therapy Lowers Blood Glucose

Proton pump inhibitor therapy is associated with improved hemoglobin A_1c levels in non-insulin-dependent Type 2 diabetes patients, based on results from two retrospective studies.

The studies, paved the way for a prospective clinical trial, which is ongoing, said Dr. Michael Crouch of the Texas and Memorial Family Medicine Residency Program, in Sugar Land.

“A graduate of our program first noticed this phenomenon in a diabetic patient when he put him on a proton pump inhibitor [PPI] for gastroesophageal reflux disease [GERD],” Dr. Crouch said in an interview. “That was the only change in medication, and the patient’s hemoglobin A_1c went down.”

Studies in the literature have shown that PPI therapy elevates gastrin levels, which in turn signal the pancreas to increase insulin production. However, this observation has never been investigated in the context of diabetes, Dr. Crouch explained.

In the first investigation, family physician Ivan Mefford of Richmond, TX, studied 347 individuals with Type 2 diabetes. None of the patients were taking insulin therapy, but they were taking either metformin monotherapy or a sulfonylurea with or without metformin and/or thiazolidenedione (Med. Hypotheses 2009;73:29-32).

Among these patients, the mean hemoglobin A_1c levels were significantly lower for those who were prescribed concomitant PPI therapy (7.0%), compared with those who were not (7.6%).

When patients were analyzed according to the type of hypoglycemic agent they were taking, mean hemoglobin A_1c levels were 6.6% among those on metformin monotherapy plus PPI’s, compared with 7.3% for those on metformin without PPI’s. Similarly, among patients on combinations of a sulfonylurea, metformin, and glitazones, those on PPI’s had a mean hemoglobin A_1c level of 6.5%, compared with 7.9% for those not on PPI’s.

In the second investigation, Dr. Crouch studied 73 similar patients, who were also on hypoglycemic agents and no exogenous insulin. A within-patient comparison showed significant differences in mean hemoglobin A_1c levels when the patients were taking PPI therapy, compared with when they were not (7.1% vs. 7.7%).

Those on metformin monotherapy, however, showed no significant differences in mean hemoglobin A_1c level with or without PPI therapy (6.81% vs. 7.1%). Among those on combination therapy, mean hemoglobin A_1c levels were significantly lower with PPI’s (7.26%) than in those who did not take PPI therapy (7.8%).

“Dr. Mefford is now looking at gastrin levels in his diabetes patients and has found that a lot of them do have low baseline levels,” said Dr. Crouch. “He’s doing a study now, taking people who don’t have GERD and prescribing a PPI to try and improve their diabetes. So far, it’s very consistent; they are responding well in about 9 out of 10 cases.”

Presented at the North American Primary Care Research Group annual meeting, Prompt CABG, Intensive Medical Therapy Effective for Type 2 Diabetes Patients With Extensive Coronary Disease