Hypoglycemia in patients with type 2 diabetes from India and Malaysia treated with sitagliptin or a sulfonylurea during Ramadan: a randomized, pragmatic study

Abstract

Objective:

To compare the incidence of symptomatic hypoglycemia between sitagliptin and sulfonylurea in Muslim patients with type 2 diabetes who fasted during Ramadan.

Methods:

In a multicenter, pragmatic, randomized study, patients with type 2 diabetes were recruited from clinical centers in India (n = 765) and Malaysia (n = 105). Eligible patients (age ≥ 18 yrs) expressed their intention to daytime fast during Ramadan, were treated with a stable dose of sulfonylurea with or without metformin for ≥3 months prior to screening visit, and had an HbA_1c ≤ 10%. Patients were randomized in a 1:1 ratio to either switch to sitagliptin 100 mg q.d. or remain on their pre-study sulfonylurea. Daily diary cards were completed to document information on hypoglycemic symptoms and complications. The primary endpoint was the overall incidence of symptomatic hypoglycemia during Ramadan.

Results:

Of the 870 patients randomized, 848 (n = 421 for sitagliptin and 427 for sulfonylurea) returned ≥1 completed diary card and were included in the analysis. The proportion of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan was lower with sitagliptin (3.8%) compared to sulfonylurea (7.3%). The risk of symptomatic hypoglycemia was significantly lower with sitagliptin (risk ratio [95% CI] = 0.52 [0.29, 0.94]; p = 0.028). By country, the proportions of patients who recorded ≥1 symptomatic hypoglycemic event during Ramadan were 4.1% vs. 7.7% in India and 1.9% vs. 3.8% in Malaysia for sitagliptin and sulfonylurea, respectively. No patient discontinued treatment due to a hypoglycemic event. One patient on sitagliptin and seven on sulfonylurea had an event that required non-medical assistance. No events required medical assistance. Both treatments were generally well tolerated.

Limitations:

Symptomatic hypoglycemic events did not require a confirmatory blood glucose measurement, which may have overestimated hypoglycemic events. Measures of glycemic control and body weight were not assessed.

Conclusion:

Switching antihyperglycemic treatment to sitagliptin from a sulfonylurea reduced the risk of symptomatic hypoglycemia by approximately 50% for Muslim patients with type 2 diabetes who fasted during Ramadan.

Clinical trial registration:

Clinicaltrials.gov: NCT01340768.

Keywords::

• Diabetes
• DPP-4 inhibitors
• Fasting
• Hypoglycemia
• Ramadan
• Sulfonylurea

Transparency

Declaration of funding

The study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA – the manufacturer of sitagliptin.

Declaration of financial/other interests

S.R.A. reported receiving grant money for his institution from MSD (Merck Sharp & Dohme Corp.), receiving consultancy fees/honoraria from MSD, travel support for an investigator meeting related to this study, and receiving payments from other pharmaceutical companies for lectures and speaker bureaus and development of education presentations. S.B.I. reported receiving grant money for his institution from MSD and receiving consultancy fees/honoraria from MSD. R.B. reported receiving grant money for his institution from MSD. J.B.G. has disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. T.Wa., S.M.L., S.S., M.J.D., C.J.G., H.L.K., L.R., S.S.E., and T.Wo. are employees of Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA and may own company stock or stock options.

CMRO peer reviewers have received honoraria for their review work on this manuscript, and have disclosed that they have no other relevant financial relationships.

Author Contributions: S.S., C.J.G., H.L.K., S.S.E., and L.R. were involved in the concept and design of the study. S.R.A., S.B.I., R.B., J.B.G., T.Wa., S.M.L., S.S., and T.Wo. were involved in the data collection and/or analysis. All authors were involved in interpretation of the results. M.J.D. drafted the article and all authors were involved in the critical revision and approval of the article.

Acknowledgments

Data management and statistical support were provided by SIRO Clinpharm Pvt Ltd (Thane, India), with funding provided by Merck Sharp & Dohme Corp.

List of study investigators by country: India. Dr. S.R. Aravind, Dr. Ramesh Babruwad, Dr. R. Balamurugan, Dr. Deepak Bhambe, Dr. Narayan Deogaonkar, Dr. Neeta Deshpande, Dr. Mala Dharmalingam, Dr. J.B. Gupta, Dr. Sandeep Kumar Gupta, Dr. Sunil Gupta, Dr. Sanjiv Indurkar, Dr. K.D. Modi, Dr. L. Sreenivasa Murthy, Dr. Sanjeev Phatak, Dr. Lilly Rodriedges, Dr. Y. Sadasivarao, Dr. Bipin Kumar Sethi, Dr. Shehla Shaikh, Dr. Paramesh Shamanna, Dr. M. Shunmugavelu. Malaysia. Prof. Shaiful Bahari Ismail, Dr. Sukumar Rajaretnam, Dr. Hamimah Saad, Dr. Narul Aida Salleh, Dr. Sri Wahyu Taher.