Doxycycline for the Treatment of Insulin Resistance in Overweight and Obese Individuals. Preliminary Data

Presentation Number: MON 589
Date of Presentation: April 3rd, 2017

Erjola Balliu*1, Margaret McNurlan2, Lorne Golub2, Joseph Schwartz2 and Marie Catherine Gelato3
1Stony Brook Hospital, Stonybrook, NY, 2Stony Brook Hospital, Stony Brook, NY, 3SUNY-Stony Brook

Abstract

Introduction: In the United States, 68.5 % of the adult population are overweight or obese and the incidence of diabetes has increased by 15% and hypertension by 10% over the last 10 years. It is imperative to find therapies to curtail this epidemic. The aim of this proof-of-concept study is to assess the pleiotropic effects of sub-microbial doses of doxycycline, including both reductions in inflammation and levels of matrix metalloproteinases, resulting in improvement in insulin resistance and hypertension.

Research Design and Methods: This is a 12 week, randomized, double-blind, placebo-controlled proof-of-concept study. The primary outcome variable is the change in insulin sensitivity from pre- to post- treatment in the group taking doxycycline compared to the group taking placebo. Insulin sensitivity will be assessed with both HOMA and the area under the curve for c-peptide during an OGTT. The secondary outcome variable is improvement in hypertension, determined by changes in central aortic pressure and arterial stiffness. In addition, the proposed study will also assess a reduction in inflammatory markers (e.g. CRP, IL6 and sTNFR2) and a reduction in circulating matrix metalloproteinases.

Results: The data presented are preliminary results on glucose metabolism only. We have arbitrarily chosen a > -5% change in fasting glucose, > -10% change in glucose AUC after OGTT and >- 2% change in HbA1c as significant. Fourteen subjects have completed the protocol. Four subjects withdrew from the study for personal conflicts. A reduction in fasting glucose and glucose AUC after a 75-g OGTT was seen in 6 subjects. Five subjects had a reduction in their HbA1c, but one of them also had unintentional weight loss of 19.2 pounds so it is not clear whether the reduction in HbA1c was from weight loss or study drug. Only 3 subjects had reduction in glycemia assessed by all 3 parameters fasting glucose, post glucose load and HbA1c. Since the study is still blinded, we do not know which of these subjects received doxycycline or placebo.

Conclusion: We speculate that the 6 subjects that improved the glycemic index by at least 2 of the 3 parameters measured could be on the doxycycline arm. These results could have enormous implications for improving the health of these at-risk individuals by retarding the progression to overt diabetes and cardiovascular disease.

 

Nothing to Disclose: EB, MM, LG, JS, MCG