1,023
Views
10
CrossRef citations to date
0
Altmetric
Review

Non-insulin pharmacological therapies for treating type 1 diabetes

, , &
Pages 947-960 | Received 02 Mar 2018, Accepted 29 May 2018, Published online: 11 Jul 2018

References

  • Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965;14:619–633.
  • Dinneen S, Alzaid A, Turk D, et al. Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM. Diabetologia. 1995;38:337–343.
  • Müller WA, Faloona GR, Aguilar-Parada E, et al. Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. N Engl J Med. 1970;283:109–115.
  • Greenbaum CJ, Prigeon RL, D’Alessio DA. Impaired beta-cell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose. Diabetes. 2002;51:951–957.
  • DCCT RG. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977–986.
  • Heller SR, Amiel SA, Mansell P. Effect of the fast-acting insulin analog lispro on the risk of nocturnal hypoglycemia during intensified insulin therapy. Diabetes Care. 1999;22:1607–1611.
  • DCCT RG. Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995;18:1415–1427.
  • Lee YH, Wang M-Y, Yu -X-X, et al. Glucagon is the key factor in the development of diabetes. Diabetologia. 2016;59:1372–1375.
  • Woerle HJ, Albrecht M, Linke R, et al. Impaired hyperglycemia-induced delay in gastric emptying in patients with type 1 diabetes deficient for islet amyloid polypeptide. Diabetes Care. 2008;31:2325–2331.
  • Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: ‘Double diabetes’ in the diabetes control and complications trial. Diabetes Care. 2007;30:707–712.
  • Conway B, Miller RG, Costacou T, et al. Temporal patterns in overweight and obesity in Type 1 diabetes. Diabet Med. 2010;27:398–404.
  • Young AA. Amylin ’ s physiology and its role in diabetes. Curr Opin Endocrinol Diabetes. 1997;4:282–290.
  • Chapman I, Parker B, Doran S, et al. Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes. Diabetologia. 2005;48:838–848.
  • Meier JJ, Nauck MA. Glucagon-like peptide 1(GLP-1) in biology and pathology. Diabetes Metab Res Rev. 2005;21:91–117.
  • Madsbad S. Prevalence of residual B cell function and its metabolic consequences in Type 1 (insulin-dependent) diabetes. Diabetologia. 1983;24:141–147.
  • Ferdinand KC, White WB, Calhoun D, et al. Effects of the Once-Weekly Glucagon-Like Peptide-1 Receptor Agonist Dulaglutide on Ambulatory Blood Pressure and Heart Rate in Patients With Type 2 Diabetes Mellitus. Hypertension. 2014;64:731–737.
  • Deacon CF. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes Metab. 2011;13:7–18.
  • Madsbad S, Krarup T, Deacon CF, et al. Glucagon-like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials. Curr Opin Clin Nutr Metab Care. 2008;11:491–499.
  • Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012;55:1577–1596.
  • Wright EM, Loo DDF, Hirayama B. Biology of human sodium glucose transporters. Physiol Rev. 2011;91:733–794.
  • Weber M, Mansfield T, Cain V, et al. Blood Pressure and Glycaemic Effects of Dapagliflozin in Patients With Type 2 Diabetes on Combination Antihypertensive Therapy: a Randomised, Placebo-controlled, Study. Lancet Diabetes Endocrinol. 2015;1. DOI:10.1016/S2213-8587(15)00417-9
  • Cariou B, Charbonnel B. Sotagliflozin as a potential treatment for type 2 diabetes mellitus. Expert Opin Investig Drugs. 2015;24:1647–1656.
  • Koda JE, Fineman M, Rink TJ, et al. Amylin concentrations and glucose control. Lancet. 1992;339:1179–1180.
  • Samsom M, Szarka LA, Camilleri M, et al. Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition. Am J Physiol Gastrointest Liver Physiol. 2000;278:G946–G51.
  • Kong MF, Stubbs T, King P, et al. The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM. Diabetologia. 1998;41:577–583.
  • Nyholm B, Ørskov L, Hove KY, et al. The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus. Metabolism. 1999;48:935–941.
  • Fineman M, Weyer C, Maggs DG, et al. The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus. Horm Metab Res. 2002;34:504–508.
  • Colburn W, Gottlieb B, Koda J, et al. Pharmacokinetics and pharmacodynamics of AC137 (25,28,29 tripro-amylin, human) after intravenous bolus and infusion doses in patients with insulin-dependent diabetes. J Clin Pharmacol. 1996;36:13–24.
  • Whitehouse F, Kruger DF, Fineman M, et al. A randomized study and open-label extension evaluating the long-term efficacy of pramlintide as an adjunct to insulin therapy in type 1 diabetes. Diabetes Care. 2002;25:724–730.
  • Ratner RE, Dickey R, Fineman M, et al. Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial. Diabet Med. 2004;21:1204–1212.
  • Edelman S, Garg S, Frias J, et al. A Double-Blind, Placebo-Controlled Trial Assessing Pramlintide Treatment in the Setting of Intensive Insulin Therapy in Type 1 Diabetes. Diabetes Care. 2006;29:2189–2195.
  • Marrero DG, Crean J, Zhang B, et al. Effect of Adjunctive Pramlintide Treatment on Treatment Satisfaction in Patients With Type 1 Diabetes. Diabetes Care. 2007;30:210–216.
  • Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409–1439.
  • Theodorakis MJ, Carlson O, Michopoulos S, et al. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab. 2006;290:E550–E9.
  • Kjems LL, Holst JJ, Vølund A, et al. The Influence of GLP-1 on Glucose-Stimulated Insulin Secretion. Diabetes. 2003;52:380–386.
  • Gutniak M, Orskov C, Holst JJ, et al. Antidiabetogenic effect of glucagon-like peptide-1 (7-36)amide in normal subjects and patients with diabetes mellitus. N Engl J Med. 1992;326:1316–1322.
  • Kielgast U, Holst JJ, Madsbad S. Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual β-cell function. Diabetes. 2011;60:1599–1607.
  • Holst JJ. Incretin hormones and the satiation signal. Int J Obes (Lond). 2013;37:1161–1168.
  • Vilsbøll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003;88:2706–2713.
  • Kuhadiya ND, Malik R, Bellini NJ, et al. Liraglutide as additional treatment to insulin in obese patients with type 1 diabetes mellitus. Endocr Pract. 2013;19:963–967.
  • Harrison LB, Mora PF, Clark GO, et al. Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs. J Investig Med. 2013;61:40–44.
  • Varanasi A, Bellini N, Rawal D, et al. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011;165:77–84.
  • Kielgast U, Krarup T, Holst JJ, et al. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function. Diabetes Care. 2011;34:1463–1468.
  • Rother KI, Spain LM, Wesley RA, et al. Effects of exenatide alone and in combination with daclizumab on beta-cell function in long-standing type 1 diabetes. Diabetes Care. 2009;32:2251–2257.
  • Hari Kumar KVS, Shaikh A, Prusty P. Addition of exenatide or sitagliptin to insulin in new onset type 1 diabetes: a randomized, open label study. Diabetes Res Clin Pract. 2013;100:e55–e8.
  • Traina AN, Lull ME, Hui AC, et al. Once-weekly exenatide as adjunct treatment of type 1 diabetes mellitus in patients receiving continuous subcutaneous insulin infusion therapy. Can J Diabetes. 2014;38:269–272.
  • Kuhadiya ND, Dhindsa S, Ghanim H, et al. Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: a Randomized Placebo-Controlled Clinical Trial of 12 Weeks. Diabetes Care. 2016;39:1027–1035.
  • Frandsen CS, Dejgaard TF, Andersen HU, et al. Twelve Weeks Treatment with Liraglutide as Add-on to Insulin in Normal-Weight Poorly Controlled Patients with Type 1 Diabetes: a Randomized, Placebo-Controlled, Double-Blind Parallel Study. Diabetes Care. 2015;38:2250–2257.
  • Dejgaard TF, Frandsen CS, Hansen TS, et al. Efficacy and safety of liraglutide for overweight adult patients with type 1 diabetes and insufficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015;8587:1–12.
  • Mathieu C, Zinman B, Uddén Hemmingsson J, et al. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: the ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes Care. 2016;39:1702–1710.
  • Ahrén B, Hirsch IB, Pieber TR, et al. Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes: the adjunct two randomized trial. Diabetes Care. 2016;39:1693–1701.
  • Pieber TR, Deller S, Korsatko S, et al. Counter-regulatory hormone responses to hypoglycaemia in people with type 1 diabetes after 4 weeks of treatment with liraglutide adjunct to insulin: a randomized, placebo-controlled, double-blind, crossover trial. Diabetes, Obes Metab. 2015;17:742–750.
  • Dubé MC, D’Amours M, Weisnagel SJ. Beyond glycaemic control: A cross-over, double-blinded, 24-week intervention with liraglutide in type 1 diabetes. Diabetes, Obes Metab. 2018;20:178–184.
  • Jendle J, Nauck MA, Matthews DR, et al. Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes, Obes Metab. 2009;11:1163–1172.
  • Jensterle M, Kravos NA, Pfeifer M, et al. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome. Hormones. 2015;14:81–90.
  • Sarkar G, Alattar M, Brown RJ, et al. Exenatide treatment for 6 months improves insulin sensitivity in adults with type 1 diabetes. Diabetes Care. 2014;37:666–670.
  • Ahrén B, Landin-Olsson M, Jansson PA, et al. Inhibition of Dipeptidyl Peptidase-4 Reduces Glycemia, Sustains Insulin Levels, and Reduces Glucagon Levels in Type 2 Diabetes. J Clin Endocrinol Metab. 2004;89:2078–2084.
  • Aaboe K, Akram S, Deacon CF, et al. Restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contributes to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors. Diabetes, Obes Metab. 2015;17:74–81.
  • Ahrén B, Charbonnel B, Wilcox RG, et al. Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care. 2007;30:1344–1350.
  • Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998;47:1663–1670.
  • Garg SK, Moser EG, Bode BW, et al. Effect of sitagliptin on post-prandial glucagon and GLP-1 levels in patients with type 1 diabetes: investigator-initiated, double-blind, randomized, placebo-controlled trial. Endocr Pract. 2012;19:19–28.
  • Farngren J, Persson M, Schweizer A, et al. Vildagliptin Reduces Glucagon during Hyperglycemia and Sustains Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes. J Clin Endocrinol Metab. 2012;97:3799–3806.
  • Ellis SL, Moser EG, Snell-Bergeon JK, et al. Effect of sitagliptin on glucose control in adult patients with Type 1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabet Med. 2011;28:1176–1181.
  • Foley JE, Ligueros-Saylan M, He YL, et al. Effect of vildagliptin on glucagon concentration during meals in patients with type 1 diabetes. Horm Metab Res. 2008;40:727–730.
  • Schopman JE, Hoekstra JBL, Frier BM, et al. Effects of sitagliptin on counterregulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double blind placebo-controlled cross-over study. Diabetes, Obes Metab. 2015;4:546–553.
  • Gorboulev V, Schürmann A, Vallon V, et al. Na +-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes. 2012;61:187–196.
  • Sands AT, Zambrowicz BP, Rosenstock J, et al. Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Diabetes Care. 2015;38:1181–1188.
  • Wilding JPH, Woo V, Rohwedder K, et al. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes, Obes Metab. 2014;16:124–136.
  • Perkins BA, Cherney DZI, Partridge H, et al. Sodium-glucose cotransporter 2 inhibition and glycemic control in type 1 diabetes: results of an 8-week open-label proof-of-concept trial. Diabetes Care. 2014;37:1480–1483.
  • Pieber TR, Famulla S, Eilbracht J, et al. Empagliflozin as adjunct to insulin in patients with type 1 diabetes: a 4-week, randomized, placebo-controlled trial (EASE-1). Diabetes Obes Metab. 2015;17:928–935.
  • Henry RR, Rosenstock J, Edelman S, et al. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015;38:412–419.
  • P, Mathieu CPhillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017;5:864–876.
  • Kuhadiya ND, Ghanim H, Mehta A, et al. Dapagliflozin as additional treatment to liraglutide and insulin in patients with type 1 diabetes. J Clin Endocrinol Metab. 2016;101:3506–3515.
  • Garg SK, Henry RR, Banks P, et al. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017;377:2337–2348.
  • Henry RR, Thakkar P, Tong C, et al. Efficacy and Safety of Canagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, as Add-On to Insulin in Patients With Type 1 Diabetes. Diabetes Care. 2015;38:dc151730.
  • Rodbard HW, Peters AL, Slee A, et al. The effect of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic end points assessed by continuous glucose monitoring and patient-reported outcomes among people with type 1 diabetes. Diabetes Care. 2017;40:171–180.
  • Cherney DZI, Perkins B, Soleymanlou N, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129:587–597.
  • Schimmack G, DeFronzo R, Musi N. AMP-activated protein kinase: role in metabolism and therapeutic implications. Diabetes, Obes Metab. 2006;8:591–602.
  • Group UP. Effects of Intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854–865.
  • Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–2443.
  • Petrie JR, Chaturvedi N, Ford I, et al. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5:597–609.
  • Vella S, Buetow L, Royle P, et al. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010;53:809–820.
  • Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment in patients with type-1 diabetes and persistent inadequate glycaemic control. A randomized study. PLoS One. 2008;3:e3363.
  • Simonson DC, Delprato S, Castellino P, et al. Effect of Glyburide on Glycemic control, insulin requirement, and glucose metabolism in insulin-treated diabetic patients. Diabetes. 1987;36:136–145.
  • Ratzmann KP, Schulz B, Heinke P, et al. Tolbutamide does not alter insulin requirement in Type 1 (insulin-dependent) diabetes. Diabetologia. 1984;27:8–12.
  • Burke BJ, Hartog M, Waterfield MR. Improved diabetic control in insulin-dependent diabetics treated with insulin and glibenclamide. Acta Endocrinol (Copenh). 1984;107:70–77.
  • Selam JL, Woertz L, Lozano J, et al. The use of glipizide combined with intensive insulin treatment for the induction of remissions in new onset adult type I diabetes. Autoimmunity. 1993;16:281–288.
  • Fallucca F, Sciullo E, Maldonato A. Combined therapy with insulin and sulfonylurea for the treatment of new-onset insulin-dependent diabetes mellitus. Horm Metab Res. 1996;28:86–88.
  • Del Prato S, Nosadini R, Tiengo, et al. Insulin mediated glucose disposal in type 1 diabetes: evidence for insulin resistance. J Clin Endocrinol Metab. 1983;57:904–910.
  • Greenfield JR, Samaras K, Chisholm DJ. Insulin resistance, intra-abdominal fat, cardiovascular risk factors, and androgens in healthy young women with type 1 diabetes mellitus. J Clin Endocrinol Metab. 2002;87:1036–1040.
  • Strowig SM, Raskin P. The effect of rosiglitazone on overweight subjects with type 1 diabetes. Diabetes Care. 2005;28:1562–1567.
  • Bhat R, Bhansali A, Bhadada S, et al. Effect of pioglitazone therapy in lean type 1 diabetes mellitus. Diabetes Res Clin Pract. 2007;78:349–354.
  • Zdravkovic V, Hamilton JK, Daneman D, et al. Pioglitazone as adjunctive therapy in adolescents with type 1 diabetes. J Pediatr. 2006;149:845–849.
  • Stone ML, Walker JL, Chisholm D, et al. The addition of rosiglitazone to insulin in adolescents with type 1 diabetes and poor glycaemic control: a randomized-controlled trial. Pediatr Diabetes. 2008;9:326–334.
  • Peyrot M, Rubin R, Lauritzen T, et al. Psychosocial problems and barriers to improved diabetes management: results of the cross-national Diabetes Attitudes, Wishes and Needs (DAWN) study. Diabetes Care. 2005;28:2673–2679.
  • Nathan DM, Cleary PA, Backlund J-YC, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643–2653.
  • Purnell JQ, Hokanson JE, Marcovina SM, et al. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. Diabetes Control and Complications Trial. JAMA. 1998;280:140–146.
  • Monnier L, Lapinski H, Colette C. Contributions of Fasting and Postprandial Plasma Glucose Increments To the Overall Diurnal Hyperglycaemia of Type 2 Diabetic Patients. Diabetes Care. 2003;26:881–885.
  • Garg S, Jovanovic L. Relationship of fasting and hourly blood glucose levels to HbA1c values: safety, accuracy, and improvements in glucose profiles obtained using a 7-day continuous glucose sensor. Diabetes Care. 2006;29:2644–2649.
  • Salehi A, Vieira E, Gylfe E. Paradoxical stimulation of glucagon secretion by high glucose concentrations. Diabetes. 2006;55:2318–2323.
  • Kohan DE, Fioretto P, Tang W, et al. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85:962–971.
  • Khouri C, Cracowski J, Roustit M. SGLT-2 inhibitors and the risk of lower-limb amputation: is this a class effect?. Diabetes Obes Metab. 2018;20:1531–1534.
  • FDA (U.S. Food and Drug Administration). FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. 2015. [cited 2018 Apr 30]. Available from: https://www.fda.gov/downloads/drugs/drugsafety/ucm475487.pdf
  • Davies MJ, Bergenstal R, Bode B, et al. Eifficacy of liraglutide for weight loss among patients with type 2 diabetes. Jama. 2015;314:687.
  • Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–2128.
  • Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–1844.
  • Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–322.
  • Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.
  • Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132:2131–2157.
  • Buteau J, El-Assaad W, Rhodes CJ, et al. Glucagon-like peptide-1 prevents beta cell glucolipotoxicity. Diabetologia. 2004;47:806–815.
  • Umapathysivam MM, Lee MY, Jones KL, et al. Comparative effects of prolonged and intermittent stimulation of the glucagon-like peptide 1 receptor on gastric emptying and glycemia. Diabetes. 2014;63:785–790.
  • Nauck M, Kemmeries G, Holst JJ, et al. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes. 2011;60:1561–1565.
  • Gough SCL, Bode B, Woo V, et al. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014;8587:1–9.
  • Buse JB, Vilsbøll T, Thurman J, et al. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014;37:2926–2933.
  • Rosenstock J, Diamant M, Aroda VR, et al. Efficacy and safety of lixilan, a titratable fixed-ratio combination of lixisenatide and insulin glargine, versus insulin glargine in type 2 diabetes inadequately controlled on metformin monotherapy: the lixilan proof-of-concept randomized trial. Diabetes Care. 2016;39:1579–1586.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.