In the Journals

Sitagliptin, lansoprazole combination affected beta cells less than expected in type 1 diabetes

A combination of sitagliptin and lansoprazole did not halt the destruction of beta-cell function in patients recently-diagnosed with type 1 diabetes, according to research published in The Lancet Diabetes & Endocrinology.

“One half of the group taking active sitagliptin and lansoprazole failed to increase the hormones on which our hypothesis was based: glucagon-like peptide-1 and gastrin,” Kurt J. Griffin, PhD, MD, told Endocrine Today.

Griffin and colleagues recruited 46 participants aged 11 to 36 years who had received a type 1 diabetes diagnosis in the previous 6 months for the year-long, double-blind, placebo-controlled REPAIR-T1D phase 2 trial.

To investigate the effects of DPP-IV inhibitors and proton-pump inhibitors (PPI) on beta survival and regeneration, the scientists divided patients — from Sanford Health Systems in Sioux Falls, South Dakota and Fargo, North Dakota, Children’s Hospitals and Clinics of Minnesota in St. Paul, and Rady Children’s Hospital in San Diego, California — into two cohorts.

Through a blocked randomization process that separated patients by streams of younger (<18 years) and older (≥18 years), and male and female, participants were assigned to oral DPP-IV inhibitor sitagliptin (50 mg for age <18 years and 100 mg for age ≥18 years) and PPI lansoprazole (30 mg for age <18 years and 60 mg for age ≥18 years) or placebo.

The researchers quantified C-peptide response to a mixed-meal challenge at 12 months by 2 hours area under the curve, based on intention to treat; 40 patients in the treatment group and 18 in placebo completed the study.

Mean change in C-peptide area under curve for the treatment group was −229 pmol/L (95% CI, −316 to −142) compared with −253 pmol/L (−383 to −123) for the placebo group. No adverse events related to treatment were observed.

“We noted a slight trend towards preservation of beta-cell function in a subgroup who produced increased concentrations of GLP-1 and gastrin while taking the study drug,” the researchers wrote.

Bearing in mind the limitations of subgroup analysis, Griffin noted the trends in those patients who did have elevated levels of the gut hormones, including preservation of C-peptide, warrants further investigation.

“We are now inviting participants to return for one additional visit to examine possible causes, including pharmacogenetics, of the variable GLP-1 and gastrin responses to the study medications.” Griffin said in an interview.  “These results will be important for the design of future trials with similar agents.”

In an accompanying commentary, Mark R, Rigby, MD, of Indiana University and Riley Hospital for Children, Indianapolis, Indiana, noted that despite not all patients experiencing the expected increase in hormones, the trend toward improved endogenous insulin secretion in those who did is of interest.

“It remains plausible that some treatments that modify hormone concentrations might increase the resilience and expansion of beta-cells, and might have a role in stabilization or remission of type 1 diabetes,” Rigby wrote. “Although DPP-IV inhibitors and GLP-1-receptor agonists could be viewed as beta-cell protective, they also increase the rate of insulin release.” — by Allegra Tiver

Disclosures: This study was funded by Sanford Research and Juvenile Diabetes Research Foundation.