Adjunct therapies in treatment of type 1 diabetes
1型糖尿病的辅助治疗
Itivrita Goyal
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Search for more papers by this authorAlamgir Sattar
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Search for more papers by this authorMegan Johnson
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Search for more papers by this authorCorresponding Author
Paresh Dandona
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Correspondence
Paresh Dandona, Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, 1000 Youngs Road, Williamsville, NY 14221.
Email: [email protected]
Search for more papers by this authorItivrita Goyal
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Search for more papers by this authorAlamgir Sattar
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Search for more papers by this authorMegan Johnson
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Search for more papers by this authorCorresponding Author
Paresh Dandona
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
Correspondence
Paresh Dandona, Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, 1000 Youngs Road, Williamsville, NY 14221.
Email: [email protected]
Search for more papers by this authorAbstract
enIn spite of developments with novel insulin preparations, novel modes of insulin delivery with insulin infusion pumps, and the facility of continuous glucose monitoring, only 20% of patients with type 1 diabetes are under adequate control. The need for innovation is clear, and, therefore, the use of adjunct therapies with other pharmacological agents currently in use for type 2 diabetes, has been tried. Currently, pramlintide is the only agent licensed for use in this condition in addition to insulin. Global trials have been conducted with liraglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), dapagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and sotagliflozin, an inhibitor of both SGLT1 and SGLT2 transporters. While dapagliflozin and sotagliflozin have now been licensed for clinical use in this condition in Europe and Japan, they have hitherto not been licensed in the United States due to a small increase in the risk of diabetic ketoacidosis. However, these agents reduce glycosylated hemoglobin (HbA1c) by 0.4%, reduce glycemic oscillations, and do not increase the risk of hypoglycemia. Liraglutide, on the other hand, induced a smaller reduction in HbA1c and thus was not considered for a license. However, further trials are currently being conducted with a combination of semaglutide, the most potent GLP-1RA, and dapagliflozin to determine whether this approach would yield better outcomes.
摘要
zh尽管有了新的胰岛素制剂, 以及胰岛素输注泵等新的给药方式和连续血糖监测设备的发展, 但只有20%的1型糖尿病患者得到充分的控制, 进一步革新的必要性是显而易见的。因此, 已有研究尝试了将2型糖尿病药物用于1型糖尿病的辅助疗法。目前, 普拉林肽是除胰岛素外唯一获准在这种情况下使用的药物。胰高血糖素样肽1受体激动剂(GLP-1RA)利拉鲁肽、钠葡萄糖共转运体2(SGLT2)抑制剂达格列净, 以及SGLT1和SGLT2转运体抑制剂索格列净已经进行了全球试验。虽然达格列净和索格列净已经在欧洲和日本获得在这种情况下的临床使用许可, 但由于糖尿病酮症酸中毒风险的小幅增加, 这些药物到目前为止还没有在美国获得许可(在1型糖尿病中的应用)。然而, 这些药物能够将糖化血红蛋白(HbA1c)水平降低0.4%, 减少了血糖波动, 并且不会增加低血糖的风险。另一方面, 利拉鲁肽降低糖化血红蛋白(HbA1c)的幅度较小, 因此并未考虑其(在1型糖尿病中的)使用许可。然而, 目前正在进行进一步的试验, 将最有效的胰高血糖素样肽1受体激动剂索马鲁肽和达格列净联合使用, 以确定这种方法是否会产生更好的结果。
CONFLICT OF INTEREST
None declared.
REFERENCES
- 1Dinneen S, Alzaid A, Turk D, Rizza R. Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM. Diabetologia. 1995; 38(3): 337-343.
- 2Miller KM, Foster NC, Beck RW, et al; T1D Exchange Clinic Network. Current state of type 1 diabetes treatment in the US: updated data from the T1D exchange clinic registry. Diabetes Care. 2015; 38(6): 971-978.
- 3McKnight JA, Wild SH, Lamb MJ, et al. Glycaemic control of type 1 diabetes in clinical practice early in the 21st century: an international comparison. Diabet Med. 2015; 32(8): 1036-1050.
- 4Lind M, Svensson AM, Kosiborod M, et al. Glycemic control and excess mortality in type 1 diabetes. N Engl J Med. 2014; 371(21): 1972-1982.
- 5Weinstock RS, Xing D, Maahs DM, et al; for the T1D Exchange Clinic Network. Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D exchange clinic registry. J Clin Endocrinol Metabol. 2013; 98(8): 3411-3419.
- 6 Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329(14): 977-986.
- 7Nathan DM, DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care. 2014; 37(1): 9-16.
- 8Lachin JM, Orchard TJ, Nathan DM, DCCT/EDIC Research Group. Update on cardiovascular outcomes at 30 years of the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2014; 37(1): 39-43.
- 9 American Diabetes Association. Adverse events and their association with treatment regimens in the diabetes control and complications trial. Diabetes Care. 1995; 18(11): 1415-1427.
- 10Davis RE, Morrissey M, Peters JR, Wittrup-Jensen K, Kennedy-Martin T, Currie CJ. Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes. Curr Med Res Opin. 2005; 21(9): 1477-1483.
- 11Harris S, Mamdani M, Galbo-Jørgensen CB, Bøgelund M, Gundgaard J, Groleau D. The effect of hypoglycemia on health-related quality of life: Canadian results from a multinational time trade-off survey. Can J Diabetes. 2014; 38(1): 45-52.
- 12Cengiz E, Xing D, Wong JC, et al; for the T1D Exchange Clinic Network. Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D exchange clinic registry. Pediatr Diabetes. 2013; 14(6): 447-454.
- 13Conway B, Miller RG, Costacou T, et al. Temporal patterns in overweight and obesity in type 1 diabetes. Diabet Med. 2010; 27(4): 398-404.
- 14Luczynski W, Szypowska A, Głowińska-Olszewska B, Bossowski A. Overweight, obesity and features of metabolic syndrome in children with diabetes treated with insulin pump therapy. Eur J Pediatr. 2011; 170(7): 891-898.
- 15Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009; 53(21): 1925-1932.
- 16 Diabetes Control and Complications Trial Research Group. Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the diabetes control and complications trial. Diabetes Care. 2001; 24(10): 1711-1721.
- 17Kilpatrick 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(3): 707-712.
- 18Purnell JQ, Zinman B, Brunzell JD. The effect of excess weight gain with intensive diabetes mellitus treatment on cardiovascular disease risk factors and atherosclerosis in type 1 diabetes mellitus: results from the diabetes control and complications trial/epidemiology of diabetes interventions and complications study (DCCT/EDIC) study. Circulation. 2013; 127(2): 180-187.
- 19Young AA. Amylin's physiology and its role in diabetes. Curr Opin Endocrinol Diabetes Obes. 1997; 4(4): 282-290.
- 20Samsom M, Szarka LA, Camilleri M, Vella A, Zinsmeister AR, Rizza RA. Pramlintide, an amylin analog, selectively delays gastric emptying: potential role of vagal inhibition. Am J Physiol Gastrointest Liver Physiol. 2000; 278(6): G946-G951.
- 21Kong MF, Stubbs TA, King P, et al. The effect of single doses of pramlintide on gastric emptying of two meals in men with IDDM. Diabetologia. 1998; 41(5): 577-583.
- 22Nyholm 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(7): 935-941.
- 23Fineman M, Weyer C, Maggs DG, Strobel S, Kolterman OG. The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus. Horm Metab Res. 2002; 34(09): 504-508.
- 24Lutz TA, Mollet A, Rushing PA, Riediger T, Scharrer E. The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats. Int J Obes (Lond). 2001; 25(7): 1005-1011.
- 25Chapman 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(5): 838-848.
- 26Whitehouse 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(4): 724-730.
- 27Ratner 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(11): 1204-1212.
- 28Edelman 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(10): 2189-2195.
- 29Nauck M. Incretin therapies: highlighting common features and differences in the modes of action of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Diabetes Obes Metab. 2016; 18(3): 203-216.
- 30Kjems LL, Holst JJ, Vølund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on β-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003; 52(2): 380-386.
- 31Holst JJ, Vilsbøll T. Combining GLP-1 receptor agonists with insulin: therapeutic rationales and clinical findings. Diabetes Obes Metab. 2013; 15(1): 3-14.
- 32Holst JJ. Incretin hormones and the satiation signal. Int J Obes (Lond). 2013; 37(9): 1161-1168.
- 33Marso SP, Daniels GH, Brown-Frandsen K, et al; LEADER Steering Committee. LEADER Trial Investigators.Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375(4): 311-322.
- 34Marso SP, Bain SC, Consoli A, et al; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375: 1834-1844.
- 35Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019; 394(10193): 121-130.
- 36Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019; 394(10193): 131-138.
- 37Kuhadiya N, Malik R, Bellini N, et al. Liraglutide as additional treatment to insulin in obese patients with type 1 diabetes mellitus. Endocr Pract. 2013; 19(6): 963-967.
- 38Harrison LB, Mora PF, Clark GO, Lingvay I. Type 1 diabetes treatment beyond insulin: role of GLP-1 analogs. J Invest Med. 2013; 61(1): 40-44.
- 39Varanasi A, Bellini N, Rawal D, et al. Liraglutide as additional treatment for type 1 diabetes. Eur J Endocrinol. 2011; 165(1): 77-84.
- 40Kielgast U, Krarup T, Holst JJ, Madsbad S. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual β-cell function. Diabetes Care. 2011; 34(7): 1463-1468.
- 41Rother KI, Spain LM, Wesley RA, et al. Effects of exenatide alone and in combination with daclizumab on β-cell function in long-standing type 1 diabetes. Diabetes Care. 2009; 32(12): 2251-2257.
- 42Kumar KH, 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(2): e55-e58.
- 43Frandsen CS, Dejgaard TF, Holst JJ, Andersen HU, Thorsteinsson B, Madsbad S. Twelve-week treatment with liraglutide as add-on to insulin in normal-weight patients with poorly controlled type 1 diabetes: a randomized, placebo-controlled, double-blind parallel study. Diabetes Care. 2015; 38(12): 2250-2257.
- 44Dejgaard 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. 2016; 4(3): 221-232.
- 45Kuhadiya 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(6): 1027-1035.
- 46Mathieu C, Zinman B, Hemmingsson JU, et al; ADJUNCT ONE Investigators. 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(10): 1702-1710.
- 47Ahren 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(10): 1693-1701.
- 48Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011; 91(2): 733-794.
- 49Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non–insulin-dependent diabetes. Diabetes. 2005; 54(12): 3427-3434.
- 50Ferrannini E, Solini A. SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Nat Rev Endocrinol. 2012; 8(8): 495-502.
- 51Ferrannini E. Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab. 2017; 26(1): 27-38.
- 52Chao EC, Henry RR. SGLT2 inhibition—a novel strategy for diabetes treatment. Nat Rev Drug Discov. 2010; 9(7): 551-559.
- 53Spatola L, Finazzi S, Angelini C, Dauriz M, Badalamenti S. SGLT1 and SGLT1 inhibitors: a role to be assessed in the current clinical practice. Diabetes Ther. 2018; 9(1): 427-430.
- 54Powell DR, Smith M, Greer J, et al. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)–mediated absorption of intestinal glucose. J Pharmacol Exp Ther. 2013; 345(2): 250-259.
- 55Zambrowicz B, Ogbaa I, Frazier K, et al. Effects of LX4211, a dual sodium-dependent glucose cotransporters 1 and 2 inhibitor, on postprandial glucose, insulin, glucagon-like peptide 1, and peptide tyrosine tyrosine in a dose-timing study in healthy subjects. Clin Ther. 2013; 35(8): 1162-1167.
- 56Powell DR, DaCosta CM, Gay J, et al. Improved glycemic control in mice lacking Sglt1 and Sglt2. Am J Physiol Endocrinol Metab. 2013; 304(2): E117-E130.
- 57Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY 3-36 physiologically inhibits food intake. Nature. 2002; 418(6898): 650-654.
- 58ambrowicz B, Freiman J, Brown PM, et al. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012; 92(2): 158-169.
- 59Rosenwasser RF, Sultan S, Sutton D, Choksi R, Epstein BJ. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab Syndr Obes. 2013; 6: 453-467.
- 60Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373(22): 2117-2128.
- 61Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377(7): 644-657.
- 62Wiviott SD, Raz I, Bonaca MP, et al; DECLARE–TIMI 58 Investigators.Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019; 380(4): 347-357.
- 63Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019; 380(24): 2295-2306.
- 64McMurray JJ, DeMets DL, Inzucchi SE, et al. A trial to evaluate the effect of the sodium–glucose co-transporter 2 inhibitor dapagliflozin on morbidity and mortality in patients with heart failure and reduced left ventricular ejection fraction (DAPA-HF). Eur J Heart Fail. 2019; 21(5): 665-675.
- 65Henry 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(3): 412-419.
- 66Perkins BA, Cherney DZ, 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(5): 1480-1483.
- 67Henry RR, Thakkar P, Tong C, Polidori D, Alba M. 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(12): 2258-2265.
- 68Pieber 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(10): 928-935.
- 69Dandona P, Mathieu C, Phillip M, et al; DEPICT-1 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study. Diabetes Care. 2018; 41(12): 2552-2559.
- 70Mathieu C, Rudofsky G, Phillip M, et al. DEPICT-2 investigators. Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial. Diabetes Obes Metab. 2020. [online ahead of print].
- 71Rosenstock J, Marquard J, Laffel LM, et al. Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE trials. Diabetes Care. 2018; 41(12): 2560-2569.
- 72Sands 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(7): 1181-1188.
- 73Garg 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(24): 2337-2348.
- 74Mathieu C, Dandona P, Phillip M, et al. Glucose variables in type 1 diabetes studies with dapagliflozin: pooled analysis of continuous glucose monitoring data from DEPICT-1 and-2. Diabetes Care. 2019; 42(6): 1081-1087.
- 75Kuhadiya ND, Ghanim H, Mehta A, et al. Dapagliflozin as additional treatment to liraglutide and insulin in patients with type 1 diabetes. J Clin Endocrinol Metabol. 2016; 101(9): 3506-3515.
- 76Garg M, Ghanim H, Kuhadiya ND, et al. Liraglutide acutely suppresses glucagon, lipolysis and ketogenesis in type 1 diabetes. Diabetes Obes Metab. 2017; 19(9): 1306-1311.
- 77 UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352(9131): 854-865.
- 78Vella S, Buetow L, Royle P, Livingstone S, Colhoun HM, Petrie JR. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010; 53(5): 809-820.
- 79Lund SS, Tarnow L, Astrup AS, et al. Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes. Diabetes Obes Metab. 2009; 11(10): 966-977.
- 80Libman IM, Miller KM, DiMeglio LA, et al. Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: a randomized clinical trial. JAMA. 2015; 314(21): 2241-2250.
- 81Petrie 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(8): 597-609.
- 82Ahren BO, Landin-Olsson M, Jansson PA, Svensson M, Holmes D, Schweizer A. Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes. J Clin Endocrinol Metabol. 2004; 89(5): 2078-2084.
- 83Aaboe K, Akram S, Deacon CF, Holst JJ, Madsbad S, Krarup T. 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(1): 74-81.
- 84Giorda CB, Nada E, Tartaglino B. Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature. Endocrine. 2014; 46(3): 406-419.
- 85Holst JJ, Deacon CF. Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes. Diabetes. 1998; 47(11): 1663-1670.
- 86Ahren B. Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care. 2007; 30(6): 1344-1350.
- 87Garg S, Moser E, Bode B, 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. 2013; 19(1): 19-28.
- 88Guo H, Fang C, Huang Y, Pei Y, Chen L, Hu J. The efficacy and safety of DPP4 inhibitors in patients with type 1 diabetes: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2016; 121: 184-191.
- 89Ellis SL, Moser EG, Snell-Bergeon JK, Rodionova AS, Hazenfield RM, Garg SK. Effect of sitagliptin on glucose control in adult patients with type 1 diabetes: a pilot, double-blind, randomized, crossover trial. Diabet Med. 2011; 28(10): 1176-1181.
- 90George PS, McCrimmon RJ. Saxagliptin co-therapy in C-peptide negative type 1 diabetes does not improve counter-regulatory responses to hypoglycaemia. Diabet Med. 2016; 33(9): 1283-1290.
- 91Farngren J, Persson M, Schweizer A, Foley JE, Ahren B. Vildagliptin reduces glucagon during hyperglycemia and sustains glucagon counterregulation during hypoglycemia in type 1 diabetes. J Clin Endocrinol Metabol. 2012; 97(10): 3799-3806.
- 92Zhao Y, Yang L, Xiang Y, et al. Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults: one year prospective study. J Clin Endocrinol Metabol. 2014; 99(5): E876-E880.