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. 2014 May;27(2):100-12.
doi: 10.2337/diaspect.27.2.100.

Novel Agents for the Treatment of Type 2 Diabetes

Ralph A DeFronzo, Curtis L Triplitt, Muhammad Abdul-Ghani, Eugenio Cersosimo

Novel Agents for the Treatment of Type 2 Diabetes

Ralph A DeFronzo et al. Diabetes Spectr. 2014 May.

Abstract

In Brief Impaired insulin secretion, increased hepatic glucose production, and decreased peripheral glucose utilization are the core defects responsible for the development and progression of type 2 diabetes. However, the pathophysiology of this disease also includes adipocyte insulin resistance (increased lipolysis), reduced incretin secretion/sensitivity, increased glucagon secretion, enhanced renal glucose reabsorption, and brain insulin resistance/neurotransmitter dysfunction. Although current diabetes management focuses on lowering blood glucose, the goal of therapy should be to delay disease progression and eventual treatment failure. Recent innovative treatment approaches target the multiple pathophysiological defects present in type 2 diabetes. Optimal management should include early initiation of combination therapy using multiple drugs with different mechanisms of action. This review examines novel therapeutic options that hold particular promise.

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Figures

Figure 1.
Figure 1.
The ominous octet. Multiple defects contribute to the development of glucose intolerance in type 2 diabetes. HGP, hepatic glucose production.
Figure 2.
Figure 2.
Pathophysiological abnormalities targeted by currently available antidiabetic medications. DPP4i, dipeptidyl peptidase-4 inhibitor; GLP1 RA, glucagon-like peptide-1 receptor agonist; HGP, hepatic glucose production; MET, metformin; SGLT2i, sodium glucose co-transporter 2 inhibitor; TZD, thiazolidinedione.
Figure 3.
Figure 3.
Insulin secretion/insulin resistance (disposition) index (ΔINS/ΔGLU ÷ IR) in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) as a function of the 2-hour plasma glucose (PG) concentration during the OGTT (see text for a more detailed discussion). ΔINS/ΔGLU = increment in plasma insulin concentration/increment in plasma glucose concentration during oral glucose tolerance testing. The curves for lean and obese individuals are shown separately. IR = insulin resistance measured with the insulin clamp technique.
See this image and copyright information in PMC

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