Skip to main content

Novel Drugs for Diabetes Therapy

  • Chapter
  • First Online:
From Obesity to Diabetes

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 274))

  • 2526 Accesses

Abstract

Since the first use of insulin 100 years ago, there have been marked improvements in diabetes therapy including, but not limited to, the development of oral antidiabetic agents (OADs), incretin mimetics and insulin analogues. Still, there are substantial shortcomings in diabetes therapy: the blood-glucose lowering effect of OADs is often limited, incretin mimetics often induce gastrointestinal side effects and insulins still induce hypoglycaemia and weight gain in many patients.

This review evaluates on-going developments of antidiabetic drugs for their potential for future therapy focussing on injectable therapies. Recent data from dual agonists, in particular tirzepatide, a combination of GIP- and GLP-1 receptor agonists, show unprecedented reductions in HbA1c, body weight and cardiovascular risk factors. Once-weekly administrations of incretin mimetics open up the potential of a combination with once-weekly insulins that have been shown to have low peak-to-trough fluctuations. Eventually, it might be feasible to administer incretins and insulins (combinations) orally. While this has already been achieved for incretins, there are still some challenges for the oral application of insulin. Nevertheless, many promising data of novel antidiabetic drugs clearly indicate that therapy of people with diabetes will become easier, safer and more efficacious in the next years.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdelmalek MF, Choi J, Kim Y, Seo K, Hompesch M (2020) HM15211, a novel GLP-1/GIP/glucagon triple-receptor co-agonist significantly reduces liver fat and body weight in obese subjects with non-alcoholic fatty liver disease: a phase 1b/2a, multi-center, randomized, placebo-controlled trial. J Hepatol 73(Suppl. 1):S124

    Article  Google Scholar 

  • Abramson A, Caffarel-Salvador E, Khang M, Dellal D, Silverstein D, Gao Y et al (2019) An ingestible self-orienting system for oral delivery of macromolecules. Science 363(6427):611–615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ambery P, Parker VE, Stumvoll M, Posch MG, Heise T, Plum-Moerschel L et al (2018) MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet 391(10140):2607–2618

    Article  CAS  PubMed  Google Scholar 

  • Baggio LL, Drucker DJ (2021) Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. Mol Metab 46:101090

    Article  CAS  PubMed  Google Scholar 

  • Bailey CJ, Day C (2018) Treatment of type 2 diabetes: future approaches. Br Med Bull 126(1):123–137

    Article  CAS  PubMed  Google Scholar 

  • Bajaj H, Isendahl J, Gowda A, Stachlewska K, Rosenstock J (2020) Efficacy and safety of switching to insulin icodec, a once-weekly basal insulin, vs insulin glargine U100 in patients with type 2 diabetes inadequately controlled on OADs and basal insulin. Diabetologia 63(Suppl. 1):657

    Google Scholar 

  • Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA (1922) Pancreatic extracts in the treatment of diabetes mellitus. Can Med Assoc J 12(3):141–146

    CAS  PubMed  PubMed Central  Google Scholar 

  • Battelino T, Bergenstal R, Rodriguez A, Fernandez Lando L, Bray R, Tong Z et al (2021) Effect of tirzepatide versus insulin degludec on glycaemic control captured with continuous glucose monitoring in patients with type 2 diabetes (SURPASS-3 CGM). Diabetologia 64(Suppl. 1):S244

    Google Scholar 

  • Becker RH, Nowotny I, Teichert L, Bergmann K, Kapitza C (2015) Low within- and between-day variability in exposure to new insulin glargine 300 U/ml. Diabetes Obes Metab 17(3):261–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bentsen MA, Rausch DM, Mirzadeh Z, Muta K, Scarlett JM, Brown JM et al (2020) Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission. Nat Commun 11(1):4458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bianzano S, Heise T, Jungnik A, Schepers C, Scholch C, Grafe-Mody U (2021) Safety, tolerability, pharmacokinetics and pharmacodynamics of single oral doses of BI 187004, an inhibitor of 11beta-hydroxysteroid dehydrogenase-1, in healthy male volunteers with overweight or obesity. Clin Diabetes Endocrinol 7(1):16

    Article  PubMed  PubMed Central  Google Scholar 

  • Boland ML, Laker RC, Mather K, Nawrocki A, Oldham S, Boland BB et al (2020) Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis. Nat Metab 2(5):413–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borner T, Geisler CE, Fortin SM, Cosgrove R, Alsina-Fernandez J, Dogra M et al (2021) GIP receptor agonism attenuates GLP-1 receptor agonist-induced nausea and emesis in preclinical models. Diabetes 70(11):2545–2553

    Article  CAS  PubMed  Google Scholar 

  • Buckley ST, Baekdal TA, Vegge A, Maarbjerg SJ, Pyke C, Ahnfelt-Ronne J et al (2018) Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med 10(467). https://doi.org/10.1126/scitranslmed.aar7047

  • Burade VS, Garcia-Ozana A, Pratley RE, Rutter GA, Vilsboll T, Thorens B et al (2021) A novel, long-acting dual agonist for GIPR/GLP-1R, HISHS-2001, demonstrates effects on HbA1c and weight loss in the db/db mouse model of type 2 diabetes. Diabetes 70(Suppl. 1):638

    Article  Google Scholar 

  • Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C et al (2020) 2019 Update to: management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 43(2):487–493

    Article  CAS  PubMed  Google Scholar 

  • Capehorn MS, Catarig AM, Furberg JK, Janez A, Price HC, Tadayon S et al (2020) Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes Metab 46(2):100–109

    Article  CAS  PubMed  Google Scholar 

  • Christensen M, Vedtofte L, Holst JJ, Vilsboll T, Knop FK (2011) Glucose-dependent insulinotropic polypeptide: a bifunctional glucose-dependent regulator of glucagon and insulin secretion in humans. Diabetes 60(12):3103–3109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB et al (2018) 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 18:3–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coskun T, Moyers JS, Roell W, O'Farrell L, Regmi A, Ruan X et al (2021) The novel GIP, GLP-1, and glucagon triple receptor agonist LY3437943 exhibits robust efficacy in preclinical models of obesity and diabetes. Diabetes 70(Suppl 1):679

    Article  Google Scholar 

  • Dahl D, Onishi Y, Norwood P, Huh R, Patel H, Rodriguez A (2021) Tirzepatide, a dual GIP/GLP-1 receptor agonist, is effective and safe when added to basal insulin for treatment of type 2 diabetes (SURPASS-5). Diabetes 70(Suppl 1):80

    Article  Google Scholar 

  • Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J et al (2021) Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet

    Google Scholar 

  • Drucker DJ (2016) Evolving concepts and translational relevance of enteroendocrine cell biology. J Clin Endocrinol Metab 101(3):778–786

    Article  CAS  PubMed  Google Scholar 

  • Dubourg J, Ueki K, Grouin JM, Fouqueray P (2021a) Efficacy and safety of imeglimin in Japanese patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Diabetes Obes Metab 23(3):800–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dubourg J, Fouqueray P, Thang C, Grouin JM, Ueki K (2021b) Efficacy and safety of Imeglimin monotherapy versus placebo in Japanese patients with type 2 diabetes (TIMES 1): a double-blind, randomized, placebo-controlled, parallel-group, multicenter phase 3 trial. Diabetes Care 44(4):952–959

    Article  CAS  PubMed  Google Scholar 

  • Eldor R, Neutel J, Homer K, Kidron M (2021) Efficacy and safety of 28-day treatment with oral insulin (ORMD-0801) in patients with type 2 diabetes: a randomized, placebo-controlled trial. Diabetes Obes Metab 23(11):2529–2538

    Article  CAS  PubMed  Google Scholar 

  • Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A et al (2021) Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet 397(10286):1736–1748

    Article  CAS  PubMed  Google Scholar 

  • Finan B, Yang B, Ottaway N, Smiley DL, Ma T, Clemmensen C et al (2015) A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med 21(1):27–36

    Article  CAS  PubMed  Google Scholar 

  • Flor A, Petrone M, Sanchez J, Petrohoy T, Jermutus L, Hansen L et al (2021) Efficacy, safety and tolerability of cotadutide as an add-on therapy in overweight subjects with type 2 diabetes treated with dapagliflozin and metformin. Diabetologia 64(Suppl. 1):S247

    Google Scholar 

  • Frias JP, Bastyr EJ 3rd, Vignati L, Tschop MH, Schmitt C, Owen K et al (2017) The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC0090-2746, in patients with type 2 diabetes. Cell Metab 26(2):343–52 e2

    Article  CAS  PubMed  Google Scholar 

  • Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK et al (2021a) Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 385(6):503–515

    Article  CAS  PubMed  Google Scholar 

  • Frias JP, Chien J, Zhang Q, Chigutsa E, Landschulz W, Wullenweber P et al (2021b) Once weekly basal insulin Fc (BIF) is safe and efficacious in patients with type 2 diabetes mellitus (T2DM) previously treated with basal insulin. J Endocr Soc 5(Suppl 1):A448–A449

    Article  PubMed Central  Google Scholar 

  • Gaich G, Chien JY, Fu H, Glass LC, Deeg MA, Holland WL et al (2013) The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab 18(3):333–340

    Article  CAS  PubMed  Google Scholar 

  • Gastaldelli A, Cusi K, Fernandez Lando L, Bray R, Brouwers B, Rodriguez A (2021) Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in patients with type 2 diabetes (SURPASS-3 MRI). Diabetologia 64(Suppl. 1):S219–SS20

    Google Scholar 

  • Gilroy CA, Capozzi ME, Varanko AK, Tong J, D'Alessio DA, Campbell JE et al (2020) Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and hyperglycemia. Sci Adv 6(35):eaaz9890

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halberg IB, Lyby K, Wassermann K, Heise T, Plum-Morschel L, Zijlstra E (2019a) The effect of food intake on the pharmacokinetics of oral basal insulin: a randomised crossover trial in healthy male subjects. Clin Pharmacokinet 58(11):1497–1504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halberg IB, Lyby K, Wassermann K, Heise T, Zijlstra E, Plum-Morschel L (2019b) Efficacy and safety of oral basal insulin versus subcutaneous insulin glargine in type 2 diabetes: a randomised, double-blind, phase 2 trial. Lancet Diabetes Endocrinol 7(3):179–188

    Article  PubMed  Google Scholar 

  • Hallakou-Bozec S, Vial G, Kergoat M, Fouqueray P, Bolze S, Borel AL et al (2021) Mechanism of action of Imeglimin: a novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab 23(3):664–673

    Article  CAS  PubMed  Google Scholar 

  • Harrison GA (1923) Insulin in alcoholic solution by the mouth. Br Med J 2(3286):1204–1205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harrison SA, Rinella ME, Abdelmalek MF, Trotter JF, Paredes AH, Arnold HL et al (2018) NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 391(10126):1174–1185

    Article  CAS  PubMed  Google Scholar 

  • Hayes MR, Borner T, De Jonghe BC (2021) The role of GIP in the regulation of GLP-1 satiety and nausea. Diabetes 70(9):1956–1961

    Article  CAS  PubMed  Google Scholar 

  • Heise T (2021a) The future of insulin therapy. Diabetes Res Clin Pract 175:108820

    Article  CAS  PubMed  Google Scholar 

  • Heise T (2021b) Tirzepatide mechanism of action: effects on endocrine function and insulin resistance in patients with type 2 diabetes. A clamp study. EASD virtual meeting. https://www.easd.org/virtualmeeting/home.html#!resources/b-tirzepatide-mechanism-of-action-effects-on-endocrine-function-and-insulin-resistance-in-patients-with-type-2-diabetes-b. Accessed 14 Nov 2021

  • Heise T, Meneghini LF (2014) Insulin stacking versus therapeutic accumulation: understanding the differences. Endocr Pract 20(1):75–83

    Article  PubMed  Google Scholar 

  • Heise T, Korsatko S, Nosek L, Coester HV, Deller S, Roepstorff C et al (2016) Steady state is reached within 2-3 days of once-daily administration of degludec, a basal insulin with an ultralong duration of action. J Diabetes 8(1):132–138

    Article  CAS  PubMed  Google Scholar 

  • Heise T, Chien J, Beals J, Benson C, Klein O, Moyers JS et al (2021) Basal insulin FC (BIF), a novel insulin suited for once weekly dosing for the treatment of patients with diabetes mellitus. J Endocr Soc 5(Suppl. 1):A329

    Article  Google Scholar 

  • Henderson SJ, Konkar A, Hornigold DC, Trevaskis JL, Jackson R, Fritsch Fredin M et al (2016) Robust anti-obesity and metabolic effects of a dual GLP-1/glucagon receptor peptide agonist in rodents and non-human primates. Diabetes Obes Metab 18(12):1176–1190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Home P (2021) The evolution of insulin therapy. Diabetes Res Clin Pract 175:108816

    Article  CAS  PubMed  Google Scholar 

  • Hope DCD, Vincent ML, Tan TMM (2021) Striking the balance: GLP-1/Glucagon Co-Agonism as a treatment strategy for obesity. Front Endocrinol (Lausanne) 12:735019

    Article  Google Scholar 

  • Hövelmann U, Brøndsted L, Kristensen NR, Ribel-Madsen R, DeVries JH, Heise T et al (2020) Insulin icodec: an insulin analog suited for once-weekly dosing in type 2 diabetes. Diabetes 69(Suppl 1):237

    Article  Google Scholar 

  • Kapitza C, Zijlstra E, Heinemann L, Castelli MC, Riley G, Heise T (2010) Oral insulin: a comparison with subcutaneous regular human insulin in patients with type 2 diabetes. Diabetes Care 33(6):1288–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kazemian P, Shebl FM, McCann N, Walensky RP, Wexler DJ (2019) Evaluation of the cascade of diabetes care in the United States, 2005-2016. JAMA Intern Med 179(10):1376–1385

    Article  PubMed  PubMed Central  Google Scholar 

  • Khedkar A, Iyer H, Anand A, Verma M, Krishnamurthy S, Savale S et al (2010) A dose range finding study of novel oral insulin (IN-105) under fed conditions in type 2 diabetes mellitus subjects. Diabetes Obes Metab 12(8):659–664

    Article  CAS  PubMed  Google Scholar 

  • Khedkar A, Lebovitz H, Fleming A, Cherrington A, Jose V, Athalye SN et al (2019) Impact of insulin Tregopil and its permeation enhancer on pharmacokinetics of metformin in healthy volunteers: randomized, open-label, placebo-controlled, crossover study. Clin Transl Sci 12(3):276–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khedkar A, Lebovitz H, Fleming A, Cherrington A, Jose V, Athalye SN et al (2020) Pharmacokinetics and pharmacodynamics of insulin Tregopil in relation to Premeal dosing time, between meal interval, and meal composition in patients with type 2 diabetes mellitus. Clin Pharmacol Drug Dev 9(1):74–86

    Article  CAS  PubMed  Google Scholar 

  • Khunti K, Millar-Jones D (2017) Clinical inertia to insulin initiation and intensification in the UK: a focused literature review. Prim Care Diabetes 11(1):3–12

    Article  PubMed  Google Scholar 

  • Kim T, Holleman CL, Nason S, Arble DM, Ottaway N, Chabenne J et al (2018a) Hepatic glucagon receptor signaling enhances insulin-stimulated glucose disposal in rodents. Diabetes 67(11):2157–2166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JK, Lee JS, Choi J, Jung SY, Lee SH, Choi IY et al (2018b) Novel combination of a long-acting GLP-1/GIP/glucagon triple agonist (HM15211) and once-weekly basal insulin (HM12460a) offers improved glucose sowering and weight loss in a diabetic animal model. Diabetes 67(Suppl 1):77

    Article  Google Scholar 

  • Kjeldsen TB, Hubalek F, Tagmose TM, Pridal L, Refsgaard HHF, Porsgaard T et al (2021) Engineering of orally available, ultralong-acting insulin analogues: discovery of OI338 and OI320. J Med Chem 64(1):616–628

    Article  CAS  PubMed  Google Scholar 

  • Kramer CK, Choi H, Zinman B, Retnakaran R (2013) Determinants of reversibility of beta-cell dysfunction in response to short-term intensive insulin therapy in patients with early type 2 diabetes. Am J Physiol Endocrinol Metab 305(11):E1398–E1407

    Article  CAS  PubMed  Google Scholar 

  • Lingvay I, Koefoed M, Stachlewska K, Hansen M, Rosenstock J (2020) Effect of three different titration algorithms of insulin icodec vs insulin glargine U100 on time in range in patients with type 2 diabetes inadequately controlled on OADs. Diabetologia 63(Suppl. 1):658

    Google Scholar 

  • Ludvik B, Giorgino F, Jodar E, Frias JP, Fernandez Lando L, Brown K et al (2021) Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet 398(10300):583–598

    Article  CAS  PubMed  Google Scholar 

  • Moyers JS, Hansen RJ, Day JW, Dickinson CD, Zhang C, Kahl SD et al (2021) Preclinical characterization of once weekly basal insulin Fc (BIF). J Endocr Soc 5(Suppl 1):A442

    Article  PubMed Central  Google Scholar 

  • Nahra R, Wang T, Gadde KM, Oscarsson J, Stumvoll M, Jermutus L et al (2021) Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomized phase 2b study. Diabetes Care 44(6):1433–1442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamura A, Terauchi Y (2015) Present status of clinical deployment of glucokinase activators. J Diabetes Investig 6(2):124–132

    Article  CAS  PubMed  Google Scholar 

  • Nauck MA, Meier JJ (2016) The incretin effect in healthy individuals and those with type 2 diabetes: physiology, pathophysiology, and response to therapeutic interventions. Lancet Diabetes Endocrinol 4(6):525–536

    Article  CAS  PubMed  Google Scholar 

  • Nauck MA, Quast DR, Wefers J, Pfeiffer AFH (2021) The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: a pathophysiological update. Diabetes Obes Metab 23(Suppl 3):5–29

    Article  CAS  PubMed  Google Scholar 

  • Nishimura E, Kjeldsen T, Glendorf FH, Stidsen CE, Hansen BF et al (2020) Molecular and biological properties of insulin icodec, a new insulin analog designed to give a long half-life suitable for once-weekly dosing. Diabetes 69(Suppl 1):236

    Article  Google Scholar 

  • Papachristou S, Popovic DS, Papanas N (2021) The new dual gastric inhibitory peptide/glucagon-like peptide 1 agonist tirzepatide in type 2 diabetes: is the future bright? Diabetes Metab Res Rev 37(8):e3503

    Article  CAS  PubMed  Google Scholar 

  • Parker VER, Robertson D, Wang T, Hornigold DC, Petrone M, Cooper AT et al (2020) Efficacy, safety, and mechanistic insights of Cotadutide, a dual receptor glucagon-like peptide-1 and glucagon agonist. J Clin Endocrinol Metab 105(3)

    Google Scholar 

  • Portron A, Jadidi S, Sarkar N, DiMarchi R, Schmitt C (2017) 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 19(10):1446–1453

    Article  CAS  PubMed  Google Scholar 

  • Pratley RE, Aroda VR, Lingvay I, Ludemann J, Andreassen C, Navarria A et al (2018) Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol 6(4):275–286

    Article  CAS  PubMed  Google Scholar 

  • Rosenstock J, Bajaj HS, Janez A, Silver R, Begtrup K, Hansen MV et al (2020) Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med 383(22):2107–2116

    Article  CAS  PubMed  Google Scholar 

  • Rosenstock J, Wysham C, Frias JP, Kaneko S, Lee CJ, Fernandez Lando L et al (2021) Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet 398(10295):143–155

    Article  CAS  PubMed  Google Scholar 

  • Ross SA (2013) Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes. Am J Med 126(9 Suppl 1):S38–S48

    Article  PubMed  Google Scholar 

  • Schmitt C, Portron A, Jadidi S, Sarkar N, DiMarchi R (2017) 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 19(10):1436–1445

    Article  CAS  PubMed  Google Scholar 

  • Silver R, Asong M, Begtrup K, Heller SR, Liu L, Rosenstock J (2021) Similar hypoglycaemia duration with once-weekly insulin icodec vs insulin glargine U100 in insulin naive or experienced patients with type 2 diabetes. Diabetologia 64(Suppl. 1):S73

    Google Scholar 

  • UK Hypoglycaemia Study Group (2007) Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 50(6):1140–1147

    Article  Google Scholar 

  • Urva S, Du Y, Thomas MK, Milicevic Z, Coskun T, Benson CT et al (2021) Novel GIP/GLP-1/glucagon receptor agonist LY3437943: a first in human dose study in healthy participants. Diabetes 70(Suppl 1):104

    Article  Google Scholar 

  • Wilson JM, Nikooienejad A, Robins DA, Roell WC, Riesmeyer JS, Haupt A et al (2020) The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diabetes Obes Metab 22(12):2451–2459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson JM, Lin Y, Luo MJ, Considine G, Cox AL, Bowsman LM et al (2021) The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: a post hoc analysis. Diabetes Obes Metab

    Google Scholar 

  • Wynne K, Park AJ, Small CJ, Meeran K, Ghatei MA, Frost GS et al (2006) Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes (Lond) 30(12):1729–1736

    Article  CAS  Google Scholar 

  • Zhang Q, Delessa CT, Augustin R, Bakhti M, Collden G, Drucker DJ et al (2021) The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling. Cell Metab 33(4):833–44 e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zijlstra E, Heinemann L, Plum-Mörschel L (2014) Oral insulin reloaded: a structured approach. J Diabetes Sci Technol 8(3):458–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Conflict of Interest

TH is shareholder of the private research institute Profil which received research funds from Adocia, Afon Technology, Astra Zeneca, Biocon, Boehringer Ingelheim, Eli Lilly, Gan Lee Pharmaceuticals, Johnson & Johnson, Julphar, Mylan, Nestlé, Neuraly, Nordic Bioscience, Novo Nordisk, Sanofi and Zealand Pharma. TH received speaker honoraria and travel grants from Eli Lilly and Novo Nordisk, and was a paid member of advisory panels for Novo Nordisk and Valbiotis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tim Heise .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Heise, T. (2022). Novel Drugs for Diabetes Therapy. In: Eckel, J., Clément, K. (eds) From Obesity to Diabetes. Handbook of Experimental Pharmacology, vol 274. Springer, Cham. https://doi.org/10.1007/164_2021_574

Download citation

Publish with us

Policies and ethics