http://informahealthcare.com/pgm ISSN: 0032-5481 (print), 1941-9260 (electronic) Postgrad Med, 2015; 127(5): 463–479 DOI: 10.1080/00325481.2015.1044756
CLINICAL FOCUS: DIABETES REVIEW
Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in combination therapy for type 2 diabetes mellitus Robert M. Guthrie
Postgraduate Medicine Downloaded from informahealthcare.com by RMIT University on 08/12/15 For personal use only.
The Ohio State University, Columbus, OH, USA Abstract
Keywords
Objective. To review the efficacy, safety, and tolerability of combination treatment regimens including a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus (T2DM). Methods. Clinical trials of combination therapies including a DPP-4 and/or SGLT2 inhibitor were identified through a PubMed database search. To be included, studies had to have a primary end point of change from baseline to ‡24 weeks in glycated hemoglobin, include ‡1 other oral antidiabetic drug (OAD), and have randomized more than 200 patients. Results were limited to medications approved by the US Food and Drug Administration at the time of the search (March 2015). Results. A total of 1534 articles for the DPP-4 inhibitor class and 434 articles for the SGLT2 inhibitor class were retrieved from PubMed. Of these, 33 articles from the DPP-4 inhibitor class and 24 articles from the SGLT2 inhibitor class were included for review. In each study, the addition of a DPP-4 or SGLT2 inhibitor as a second or third agent resulted in improved glycemic control versus comparator arms. Reductions in weight or lack of weight gain were consistently observed, as were low rates of hypoglycemic events, particularly when the combination regimen also included metformin. Overall, the pattern of adverse events observed in combination treatment groups was consistent with the known effects of the individual agents. Conclusion. Combination treatment with a DPP-4 and/or SGLT2 inhibitor is an efficacious option for patients with T2DM starting pharmacological therapy, or for patients who have received treatment but require additional glycemic control. Study findings indicate that the underlying mechanisms of action of DPP-4 inhibitors and SGLT2 inhibitors complement a variety of OADs.
Combination therapy, dipeptidyl peptidase-4 inhibitor, metformin, sodium-glucose cotransporter 2 inhibitor, type 2 diabetes mellitus
Introduction Diabetes is a growing epidemic. The prevalence of diabetes in the United States nears 30 million, and future projections estimate that one in three adults could have diabetes by 2050 if current trends continue [1]. Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and progressive b-cell dysfunction [2], accounts for >90% of diagnosed cases [3]. The association between chronic hyperglycemia and the development of vascular complications has been established [2]. Strict glycemic control may help reduce the risk of microvascular complications and correct the pathophysiological damage chronic hyperglycemia exerts on b-cells and insulin secretion [2]. Guidelines from the American Diabetes Association (ADA) are based on a stepwise approach to establish glycemic control [4]. For most adults with T2DM, a glycated hemoglobin (HbA1c) goal of
CLINICAL FOCUS: DIABETES REVIEW
Clinical use of dipeptidyl peptidase-4 and sodium-glucose cotransporter 2 inhibitors in combination therapy for type 2 diabetes mellitus Robert M. Guthrie
Postgraduate Medicine Downloaded from informahealthcare.com by RMIT University on 08/12/15 For personal use only.
The Ohio State University, Columbus, OH, USA Abstract
Keywords
Objective. To review the efficacy, safety, and tolerability of combination treatment regimens including a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or sodium-glucose cotransporter 2 (SGLT2) inhibitor for type 2 diabetes mellitus (T2DM). Methods. Clinical trials of combination therapies including a DPP-4 and/or SGLT2 inhibitor were identified through a PubMed database search. To be included, studies had to have a primary end point of change from baseline to ‡24 weeks in glycated hemoglobin, include ‡1 other oral antidiabetic drug (OAD), and have randomized more than 200 patients. Results were limited to medications approved by the US Food and Drug Administration at the time of the search (March 2015). Results. A total of 1534 articles for the DPP-4 inhibitor class and 434 articles for the SGLT2 inhibitor class were retrieved from PubMed. Of these, 33 articles from the DPP-4 inhibitor class and 24 articles from the SGLT2 inhibitor class were included for review. In each study, the addition of a DPP-4 or SGLT2 inhibitor as a second or third agent resulted in improved glycemic control versus comparator arms. Reductions in weight or lack of weight gain were consistently observed, as were low rates of hypoglycemic events, particularly when the combination regimen also included metformin. Overall, the pattern of adverse events observed in combination treatment groups was consistent with the known effects of the individual agents. Conclusion. Combination treatment with a DPP-4 and/or SGLT2 inhibitor is an efficacious option for patients with T2DM starting pharmacological therapy, or for patients who have received treatment but require additional glycemic control. Study findings indicate that the underlying mechanisms of action of DPP-4 inhibitors and SGLT2 inhibitors complement a variety of OADs.
Combination therapy, dipeptidyl peptidase-4 inhibitor, metformin, sodium-glucose cotransporter 2 inhibitor, type 2 diabetes mellitus
Introduction Diabetes is a growing epidemic. The prevalence of diabetes in the United States nears 30 million, and future projections estimate that one in three adults could have diabetes by 2050 if current trends continue [1]. Type 2 diabetes mellitus (T2DM), characterized by insulin resistance and progressive b-cell dysfunction [2], accounts for >90% of diagnosed cases [3]. The association between chronic hyperglycemia and the development of vascular complications has been established [2]. Strict glycemic control may help reduce the risk of microvascular complications and correct the pathophysiological damage chronic hyperglycemia exerts on b-cells and insulin secretion [2]. Guidelines from the American Diabetes Association (ADA) are based on a stepwise approach to establish glycemic control [4]. For most adults with T2DM, a glycated hemoglobin (HbA1c) goal of
