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Review

Dual GIP–GLP1-Receptor Agonists In The Treatment Of Type 2 Diabetes: A Short Review On Emerging Data And Therapeutic Potential

ORCID Icon &
Pages 1973-1985 | Published online: 30 Sep 2019

References

  • Reaven GM . HOMA-beta in the UKPDS and ADOPT. Is the natural history of type 2 diabetes characterised by a progressive and inexorable loss of insulin secretory function? Maybe? Maybe not? Diab Vasc Dis Res . 2009;6(2):133–138. doi:10.1177/1479164109336038 20368203
  • American Diabetes Association. Pharmacologic approaches to glycemic treatment. Diabetes Care . 2017;40 Suppl 1:S64–S74. doi:10.2337/dc17-er07b
  • Fosse-Edorh S , Fagot-Campagna A , Detournay B , et al. Impact of socio-economic position on health and quality of care in adults with type 2 diabetes in France: the entred 2007 study. Diabet Med . 2015;32(11):1438–1444. doi:10.1111/dme.12783 25884777
  • Clemmensen C , Finan B , Müller TD , DiMarchi RD , Tschöp MH , Hofmann SM . Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases. Nat Rev Endocrinol . 2019;15(2):90–104. doi:10.1038/s41574-018-0118-x 30446744
  • Vague J . The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr . 1956;4(1):20–34. doi:10.1093/ajcn/4.1.20 13282851
  • Reilly SM , Saltiel AR . Adapting to obesity with adipose tissue inflammation. Nat Rev Endocrinol . 2017;13(11):633–643. doi:10.1038/nrendo.2017.90 28799554
  • Kumari M , Heeren J , Scheja L . Regulation of immunometabolism in adipose tissue. Semin Immunopathol . 2018;40(2):189–202. doi:10.1007/s00281-017-0668-3 29209828
  • Matthews DR , Cull CA , Stratton IM , Holman RR , Turner RC . UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med . 1998;15(4):297–303. doi:10.1002/(SICI)1096-9136(199804)15:4<297::AID-DIA572>3.0.CO;2-W 9585394
  • Levy J , Atkinson AB , Bell PM , McCance DR , Hadden DR . Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med . 1998;15(4):290–296. doi:10.1002/(SICI)1096-9136(199804)15:4<290::AID-DIA570>3.0.CO;2-M 9585393
  • Lean MEJ , Leslie WS , Barnes AC , et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol . 2019;7(5):344–355. doi:10.1016/S2213-8587(19)30068-3 30852132
  • Lim EL , Hollingsworth KG , Aribisala BS , Chen MJ , Mathers JC , Taylor R . Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011;54(10):2506–2514. doi:10.1007/s00125-011-2204-7 21656330
  • Brunzell JD , Robertson RP , Lerner RL , et al. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab . 1976;42(2):222–229. doi:10.1210/jcem-42-2-222 1262429
  • O’Rahilly S , Turner RC . Matthews DR Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes. N Engl J Med . 1988;318(19):1225–1230. doi:10.1056/NEJM198805123181902 3283553
  • Pimenta W , Korytkowski M , Mitrakou A , et al. Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. JAMA . 1995;273(23):1855–1861.7776502
  • Nauck M , Stöckmann F , Ebert R , Creutzfeldt W . Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia . 1986;29(1):46–52. doi:10.1007/bf02427280 3514343
  • Nauck MA , Meier JJ . The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol . 2016;4(6):525–536. doi:10.1016/S2213-8587(15)00482-9 26876794
  • Jörnvall H , Carlquist M , Kwauk S , et al. Amino acid sequence and heterogeneity of gastric inhibitory polypeptide (GIP). FEBS Lett . 1981;123(2):205–210. doi:10.1016/0014-5793(81)80288-8 7227513
  • Lund PK , Goodman RH , Montminy MR , Dee PC . Habener JF Anglerfish islet pre-proglucagon II. Nucleotide and corresponding amino acid sequence of the cDNA. J Biol Chem . 1983;258(5):3280–3284.6338015
  • Gutniak M , Orskov C , Holst JJ , Ahrén B , Efendic S . Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med . 1992;326(20):1316–1322. doi:10.1056/NEJM199205143262003 1348845
  • Willms B , Werner J , Holst JJ , Orskov C , Creutzfeldt W , Nauck MA . Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients. J Clin Endocrinol Metab . 1996;81(1):327–332. doi:10.1210/jcem.81.1.8550773 8550773
  • Vilsbøll T , Krarup T , Madsbad S , Holst JJ . Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia . 2002;45(8):1111–1119. doi:10.1007/s00125-002-0878-6 12189441
  • Nauck MA , Heimesaat MM , Orskov C , Holst JJ , Ebert R , Creutzfeldt W . Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest . 1993;91(1):301–307. doi:10.1172/JCI116186 8423228
  • Gault VA , O’Harte FP , Harriott P , Flatt PR . Characterization of the cellular and metabolic effects of a novel enzyme-resistant antagonist of glucose-dependent insulinotropic polypeptide. Biochem Biophys Res Commun . 2002;290(5):1420–1426. doi:10.1006/bbrc.2002.6364 11820780
  • Gault VA , Irwin N , Green BD , et al. Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. Diabetes . 2005;54(8):2436–2446. doi:10.2337/diabetes.54.8.2436 16046312
  • Miyawaki K , Yamada Y , Ban N , et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med . 2002;8(7):738–742. doi:10.1038/nm727 12068290
  • Jones IR , Owens DR , Luzio S , Williams S , Hayes TM . The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia . 1989;32(9):668–677. doi:10.1007/bf00274255 2676668
  • Toft-Nielsen MB , Damholt MB , Madsbad S , et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab . 2001;86(8):3717–3723. doi:10.1210/jcem.86.8.7750 11502801
  • Nauck MA , Vardarli I , Deacon CF , Holst JJ , Meier JJ . Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down? Diabetologia . 2011;54(1):10–18. doi:10.1007/s00125-010-1896-4 20871975
  • Vilsbøll T , Krarup T , Madsbad S , Holst JJ . Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept . 2003;114(2–3):115–121. doi:10.1016/s0167-0115(03)00111-3 12832099
  • Nauck MA , Bartels E , Orskov C , Ebert R , Creutzfeldt W . Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7-36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. J Clin Endocrinol Metab . 1993;76(4):912–917. doi:10.1210/jcem.76.4.8473405 8473405
  • Edwards CM , Todd JF , Mahmoudi M , et al. Glucagon-like peptide 1 has a physiological role in the control of postprandial glucose in humans: studies with the antagonist exendin 9-39. Diabetes . 1999;48(1):86–93.9892226
  • Finan B , Ma T , Ottaway N , et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med . 2013;5(209):209ra151. doi:10.1126/scitranslmed.3007218
  • Kjems LL , Holst JJ , Vølund A , Madsbad S . The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes . 2003;52(2):380–386. doi:10.2337/diabetes.52.2.380 12540611
  • Højberg PV , Vilsbøll T , Rabøl R , et al. Madsbad S Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia . 2009;52(2):199–207. doi:10.1007/s00125-008-1195-5 19037628
  • Mroz PA , Finan B , Gelfanov V , et al. Optimized GIP analogs promote body weight lowering in mice through GIPR agonism not antagonism. Mol Metab . 2019;20:51–62. doi:10.1016/j.molmet.2018.12.001 30578168
  • Campbell JE , Ussher JR , Mulvihill EE , et al. TCF1 links GIPR signaling to the control of beta cell function and survival. Nat Med . 2016;22(1):84–90. doi:10.1038/nm.3997 26642437
  • Widenmaier SB , Kim SJ , Yang GK , et al. A GIP receptor agonist exhibits beta-cell anti-apoptotic actions in rat models of diabetes resulting in improved beta-cell function and glycemic control. PLoS One . 2010;5(3):e9590. doi:10.1371/journal.pone.0009590 20231880
  • Hasib A , Ng MT , Gault VA , et al. An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice. Diabetologia . 2017;60(3):541–552. doi:10.1007/s00125-016-4186-y 28004148
  • Coskun T , Sloop KW , Loghin C , et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Mol Metab ;2018 3–14. doi:10.1016/j.molmet.2018.09.009
  • Tschöp MH , Finan B , Clemmensen C , et al. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab . 2016;24(1):51–62. doi:10.1016/j.cmet.2016.06.021 27411008
  • Portron A , Jadidi S , Sarkar N , DiMarchi R , Schmitt C . Pharmacodynamics, pharmacokinetics, safety and tolerability of the novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist RG7697 after single subcutaneous administration in healthy subjects. Diabetes Obes Metab . 2017;19(10):1446–1453. doi:10.1111/dom.13025 28741871
  • Schmitt C , Portron A , Jadidi S , Sarkar N , DiMarchi R . Pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of the novel dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist RG7697 in people with type 2 diabetes mellitus. Diabetes Obes Metab . 2017;19(10):1436–1445. doi:10.1111/dom.13024 28730694
  • Frias JP , Bastyr EJ 3rd , Vignati L , et al. The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC0090-2746, in patients with type 2 diabetes. Cell Metab . 2017;26(2):343–352. doi:10.1016/j.cmet.2017.07.011 28768173
  • Frias JP , Nauck MA , Van J , et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet . 2018;392(10160):2180–2193. doi:10.1016/S0140-6736(18)32260-8 30293770
  • Bokvist K , Brown R , Coskun T , et al. LY3298176, a novel long-acting GIP/GLP-1 coagonist, shows enhanced activity on weight loss and energy utilization whilst maintaining its efficacy for glycaemic control. Diabetologia . 2017;60(suppl 1):S399.