Incretin-Based Therapies
Viewpoints on the way to consensus
- Michael. A. Nauck, MD1,
- Tina Vilsbøll, MD2,
- Baptist Gallwitz, MD3,
- Alan Garber, MD4 and
- Sten Madsbad, MD5
- 1Diabetes Center Bad Lauterberg, Bad Lauterberg im Harz, Germany;
- 2Department of Internal Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark;
- 3Department of Medicine IV, Eberhard-Karls University Tübingen, Tübingen, Germany;
- 4Division of Diabetes, Endocrinology & Metabolism, Baylor College of Medicine, Houston, Texas;
- 5Department of Endocrinology, Hvidovre University Hospital, University of Copenhagen, Copenhagen, Denmark.
- Corresponding author: Michael A. Nauck, m.nauck{at}diabeteszentrum.de.
Article Figures & Tables
Figures
- Figure 1
Schematic diagram explaining the physiological (postprandial) secretion of GLP-1 from the gut, its binding to GLP-1 receptors (e.g., on pancreatic endocrine β-cells), and its degradation by the ubiquitous protease DPP-4 as well as its rapid renal elimination (A). Incretin mimetics are peptide GLP-1 receptor agonists more or less structurally similar to GLP-1, which bind and activate the GLP-1 receptor, but are not degraded by DPP-4 and have much slower elimination pharmacokinetics (B). DPP-4 inhibitors prevent the degradation/inactivation of the biologically active form of GLP-1 and, thereby, augment the biological activity of GLP-1 released from endogenous sources (C).
Tables
- Table 1
Similarities of incretin-based therapies
Properties/action Incretin mimetics DPP-4 inhibitors Glucose-dependent insulin secretion Yes Yes Glucose-dependent glucagonostatic effect Yes Yes Effect on fasting plasma glucose (reduction) By 1.4–3.4 mmol/l By 1.0–1.4 mmol/l Effect on postprandial glucose Yes Yes (but weaker) Effect on A1C (reduction) By 0.8–1.8% By 0.5–1.1% Effect on (pro)insulin biosynthesis Yes Yes (weaker?) Improved in vivo β-cell function (in humans) Yes* Yes* Beneficial cardiovascular effects Probable Not proven -
↵*As determined while patients received treatment (lasting effects need to be proven after washing out treatment).
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- Table 2
Differences of incretin-based therapies
Properties/action Incretin mimetics DPP-4 inhibitors Administration Subcutaneous Oral GLP-1 levels (or equivalent) Pharmacological (six- to tenfold) Physiological (two- to threefold) Main mechanism of GLP-1 receptor stimulation Interaction with receptors on target organs/cells Interaction with receptors on afferent nerves (autonomous nervous system) Other mediators No GIP, PACAP, others (questionable) Effects on gastric emptying Yes No (hardly) Effects on appetite Reduced Hardly influenced Effects on body weight Weight loss Weight neutrality Adverse events Nausea, vomiting, antibodies (exenatide, relevance?), pancreatitis (causal relation?) Upper respiratory tract infections, elevations in liver enzymes (vildagliptin), skin reactions (sitagliptin)
