New therapies for diabesity
- Clifford J. Bailey
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Many patients with type 2 diabetes are obese (diabesity), and the two conditions together impose a particularly complex therapeutic challenge. Several differently acting agents are often required at the same time, encouraging development of more single-tablet combinations. Longer-acting (once daily and once weekly) injected agonists of glucagon-like peptide-1 are due to provide additional options to stimulate insulin secretion with weight loss and minimal risk of hypoglycemia. Further, dipeptidyl peptidase-4 inhibitors (“weight-neutral” insulinotropic agents) are also expected. Sodium-glucose cotransporter 2 inhibitors offer a new option to reduce hyperglycemia and facilitate weight loss by increasing the elimination of glucose in the urine. Selective peroxisome proliferator-activated receptor modulators are being studied to produce compounds with desired effects. Many other agents with antidiabetic and antiobesity activity are progressing in clinical development.
- Bailey CJ: Drugs on the horizon for diabesity. Curr Diab Rep 2005, 5:353–359. CrossRef
- Shafrir E: Animal models for non-insulin-dependent diabetes. Diabetes Metab Rev 1992, 8:179–208. CrossRef
- Kahn SE, Hull RL, Utzschneider KM: Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006, 444:840–846. CrossRef
- Montague CT, O’Rahilly S: The perils of portliness. Causes and consequences of visceral adiposity. Diabetes 2000, 49:883–888. CrossRef
- Maggio CA, Pi-Sunyer FX: Obesity and type 2 diabetes. Endocrinol Metab Clin North Am 2003, 32:805–822. CrossRef
- Aucott L, Poobalan A, Smith WC, et al.: Weight loss in obese diabetic and non-diabetic individuals and long-tem diabetes outcomes—a systematic review. Diabetes Obes Metab 2004, 6:85–94. CrossRef
- Krentz AJ, Bailey CJ: Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs 2005, 65:385–411. CrossRef
- Bailey CJ, Day C: Fixed-dose single tablet antidiabetic combinations. Whence and whither the fixed-dose combination? Diabetes Obes Metab 2009, 11:527–533. CrossRef
- Wald NJ, Law MR: A strategy to reduce cardiovascular disease by more than 80%. BMJ 2003, 326:1419–1423. CrossRef
- Holst JJ: Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia 2006, 49:253–260. CrossRef
- Gentilella R, Bianchi C, Rossi A, Rotella CM: Exenatide: a review from pharmacology to clinical practice. Diabetes Obes Metab 2009, 11:544–556. CrossRef
- Garber A, Henry R, Ratner R, et al.: Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009, 373:473–481. CrossRef
- Flatt PR, Bailey CJ, Green BD: Recent advances in antidiabetic drug therapies targeting the enteroinsular axis. Curr Drug Metab 2009, 10:125–137. CrossRef
- Pan CQ, Buxton JM, Yung SL, et al.: Design of a long-acting peptide functioning as both a glucagon-like peptide-1 receptor agonist and a glucagon receptor antagonist. J Biol Chem 2006, 281:12506–12515. CrossRef
- Chen D, Liao J, Li N, et al.: A nonpeptidic agonist of glucagon-like peptide-1 receptors with efficacy in diabetic db/db mice. Proc Natl Acad Sci U S A 2007, 104:943–948. CrossRef
- Knudsen LB, Kiel D, Teng M, et al.: Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc Natl Acad Sci U S A 2007, 104:937–942. CrossRef
- Flatt PR: Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity-diabetes? Diabet Med 2008, 25:759–764. CrossRef
- Irwin N, McClean PL, O’Harte FP, et al.: Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist (Pro3)GIP prevents the development of diabetes and related metabolic abnormalities associated with genetically inherited obesity in ob/ob mice. Diabetologia 2007, 50:1532–1540. CrossRef
- Flatt PR, Bailey CJ, Green BD: Dipeptidyl peptidase IV (DPP IV) and related molecules in type 2 diabetes. Front Biosci 2008, 13:3648–3660. CrossRef
- Berger JP, Akiyama TE, Meinke PT: PPARs: therapeutic targets for metabolic disease. Trends Pharmacol Sci 2005, 26:244–251. CrossRef
- Quinn CE, Hamiltoon PK, Lockhart CJ, McVeigh GE: Thiazolidinediones: effects on insulin resistance and cardiovascular system. Br J Pharmacol 2008, 153:636–645. CrossRef
- Gross B, Staels B: PPAR agonists: multimodal drugs for the treatment of type 2 diabetes. Clin Endocrinol Metab 2007, 21:687–710.
- Allen T, Zhang F, Moodle SA, et al.: Halofenate is a selective peroxisome proliferators-activated receptor gamma modulator with antidiabetic activity. Diabetes 2006, 55:2523–2533. CrossRef
- Puigserver P, Spegelman BM: Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003, 24:78–90. CrossRef
- Conlon D: Goodbye glitazars? Br J Diabetes Vasc Dis 2006, 6:135–137. CrossRef
- Evans RM, Barish GD, Wang YX: PPARs and the complex journey to obesity. Nat Med 2004, 10:1–7. CrossRef
- Jabbour SA, Goldstein BJ: Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes. Int J Clin Pract 2008, 62:1279–1284. CrossRef
- Bailey CJ, Gross JL, Bastone L, et al.: Dapagliflozin as an add-on to metformin lowers hyperglycaemia in type 2 diabetes patients inadequately controlled with metformin alone. Diabetologia 2009, 52:A169. CrossRef
- Zhang B, Salituro G, Szalkowski D, et al.: Discovery of a small molecule insulin mimetic with antidiabetic activity in mice. Science 1999, 284:974–977. CrossRef
- Koren S, Fantus IG: Inhibition of the protein tyrosine phosphatase PTP1B: potential therapy for obesity, insulin resistance and type 2 diabetes mellitus. Clin Endocrinol Metab 2007, 21:621–640.
- Bailey CJ: Treating insulin resistance: future prospects. Diabetes Vasc Dis Res 2007, 4:20–31. CrossRef
- Matschinsky FM, Magnuson MA, Zelent D, et al.: The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapy. Diabetes 2006, 55:1–12. CrossRef
- Agius L: New hepatic targets for glycaemic control in diabetes. Clin Endocrinol Metab 2007, 21:587–606.
- Schimmack G, DeFronzo RA, Musi N: AMP-activated protein kinase: role in metabolism and therapeutic implications. Diabetes Obes Metab 2006, 8:591–602. CrossRef
- Rivera N, Everett-Grueter CA, Edgerton DS, et al.: A novel glucagon receptor antagonist, NNC 15-0926, blunts hepatic glucose production in the conscious dog. J Pharm Exp Ther 2007, 321:743–752. CrossRef
- Jacobson PB, von Geldern TW, Ohman L, et al.: Hepatic glucocorticoid antagonism is sufficient to reduce elevated hepatic glucose output and improve glucose control in animal models of type 2 diabetes. J Pharm Exp Ther 2005, 314:191–200. CrossRef
- Tomlinson JW, Stewart PM: Modulation of glucocorticoid action and the treatment of type 2 diabetes. Clin Endocrinol Metab 2007, 21:607–619.
- Pijl H, Ohashi S, Matsuda M, et al.: Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care 2000, 23:1154–161. CrossRef
- Bailey CJ: New drugs for the treatment of diabetes mellitus. In International Textbook of Diabetes Mellitus, edn 3. Edited by DeFronzo RA, Ferrannini E, Keen H, Zimmet P. Chichester: John Wiley; 2004:951–980.
- Di Marzo V: The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 2008, 51:1356–1367. CrossRef
- Rosenstock J, Hollander P, Chevalier S, et al.: The Serenade trial: effect of monotherapy with rimonabant, the first selective CB1 receptor antagonist, on glycemic control, body weight and lipid profile in drug-naïe type 2 diabetes. Diabetes Care 2008, 31:2169–2176. CrossRef
- Christensen R, Kristensen P, Bartels EM, et al.: Efficacy and safety of the weight loss drug rimonabant: a meta-analysis of randomised trials. Lancet 2007, 370:1706–1713. CrossRef
- Day C, Bailey CJ: Pharmacological approaches to reduce adiposity. Br J Diabetes Vasc Dis 2006, 6:121–125. CrossRef
- Kruger DF, Gloster MA: Pramlintide for the treatment of insulin-requiring diabetes mellitus: rationale and review of clinical data. Drugs 2004, 64:1419–1432. CrossRef
- Bailey CJ, Day C: New pharmacological approaches to obesity. Obes Pract 2005, 1:2–5.
- Billyard T, McTernan P, Kumar S: Potential therapies based on antidiabetic peptides. Clin Endocrinol Metab 2007, 21:641–655.
- Kadowski T, Yamauchi T: Adiponectin and adiponectin receptors. Endocr Rev 2005, 26:439–451. CrossRef
- Graham TE, Yang Q, Bluher M, et al.: Retinal binding protein 4 and insulin resistance in lean, obese and diabetic subjects. N Engl J Med 2006, 354:2552–2563. CrossRef
- Lavu S, Boss O, Elliott PJ, Lambert PD: Sirtuins: novel therapeutic targets to treat age-associated diseases. Nat Rev Drug Discov 2008, 7:841–853. CrossRef
- Milne JC, Lambert PD, Schenk S, et al.: Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 2007, 450:712–716. CrossRef
- New therapies for diabesity
Current Diabetes Reports
Volume 9, Issue 5 , pp 360-367
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- Current Science Inc.
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- Author Affiliations
- 1. Life and Health Sciences, Aston University, Aston Street, Aston Triangle, Birmingham, B4 7ET, UK