Liraglutide Therapy in a Prediabetic State: Rethinking the Evidence

Author(s): Georgios S. Papaetis*

Journal Name: Current Diabetes Reviews

Volume 16 , Issue 7 , 2020

Become EABM
Become Reviewer
Call for Editor


Background: Prediabetes is defined as a state of glucose metabolism between normal glucose tolerance and type 2 diabetes. Continuous β-cell failure and death are the reasons for the evolution from normal glucose tolerance to prediabetes and finally type 2 diabetes.

Introduction: The necessity of new therapeutic approaches in order to prevent or delay the development of type 2 diabetes is obligatory. Liraglutide, a long-acting GLP-1 receptor agonist, has 97% homology for native GLP-1. Identification of the trophic and antiapoptotic properties of liraglutide in preclinical studies, together with evidence of sustained β-cell function longevity during its administration in type 2 diabetes individuals, indicated its earliest possible administration during this disease, or even before its development, so as to postpone or delay its onset.

Methods: Pubmed and Google databases have been thoroughly searched and relevant studies were selected.

Results: This paper explores the current evidence of liraglutide administration both in humans and animal models with prediabetes. Also, it investigates the safety profile of liraglutide treatment and its future role to postpone or delay the evolution of type 2 diabetes.

Conclusion: Liralgutide remains a valuable tool in our therapeutic armamentarium for individuals who are overweight or obese and have prediabetes. Future well designed studies will give valuable information that will help clinicians to stratify individuals who will derive the most benefit from this agent, achieving targeted therapeutic strategies.

Keywords: Prediabetes, impaired fasting glucose, impaired glucose tolerance, glucagon-like peptide-1, glucagon-like peptide-1 receptor agonists, liraglutide.

Papaetis GS, Papakyriakou P, Panagiotou TN. Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns. Arch Med Sci 2015; 11(3): 463-82.
[] [PMID: 26170839]
Papaetis GS, Orphanidou D, Panagiotou TN. Thiazolidinediones and type 2 diabetes: from cellular targets to cardiovascular benefit. Curr Drug Targets 2011; 12(10): 1498-512.
[] [PMID: 21675944]
Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia 2019; 62(1): 3-16.
[] [PMID: 30171279]
Loizou T, Pouloukas S, Tountas C, Thanopoulou A, Karamanos V. An epidemiologic study on the prevalence of diabetes, glucose intolerance, and metabolic syndrome in the adult population of the Republic of Cyprus. Diabetes Care 2006; 29(7): 1714-5.
[] [PMID: 16801614]
American Diabetes Association. 2 Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019 Diabetes Care. 2019; 42(Suppl. 1): S13-28.
[] [PMID: 30559228]
Papaetis GS. Incretin-based therapies in prediabetes: Current evidence and future perspectives. World J Diabetes 2014; 5(6): 817-34.
[] [PMID: 25512784]
Kanat M, Winnier D, Norton L, et al. The relationship between beta-cell function and glycated hemoglobin: results from the veterans administration genetic epidemiology study. Diabetes Care 2011; 34(4): 1006-10.
[] [PMID: 21346184]
Perreault L, Færch K. Approaching pre-diabetes. J Diabetes Complications 2014; 28(2): 226-33.
[] [PMID: 24342268]
Kanat M, DeFronzo RA, Abdul-Ghani MA. Treatment of prediabetes. World J Diabetes 2015; 6(12): 1207-22.
[] [PMID: 26464759]
Kahn SE, Zraika S, Utzschneider KM, Hull RL. The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia 2009; 52(6): 1003-12.
[] [PMID: 19326096]
Creutzfeldt W. The incretin concept today. Diabetologia 1979; 16(2): 75-85.
[] [PMID: 32119]
Nauck MA, Homberger E, Siegel EG, et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab 1986; 63(2): 492-8.
[] [PMID: 3522621]
Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia 2006; 49(2): 253-60.
[] [PMID: 16416146]
Højberg PV, Vilsbøll T, Rabøl R, et al. 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.
[] [PMID: 19037628]
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): 10-8.
[] [PMID: 20871975]
Larsen MP, Torekov SS. Glucagon-Like Peptide 1: A Predictor of Type 2 Diabetes? J Diabetes Res 2017; 20177583506
[] [PMID: 29082261]
Rask E, Olsson T, Söderberg S, et al. Insulin secretion and incretin hormones after oral glucose in non-obese subjects with impaired glucose tolerance. Metabolism 2004; 53(5): 624-31.
[] [PMID: 15131768]
Fritsche A, Stefan N, Hardt E, Häring H, Stumvoll M. Characterisation of beta-cell dysfunction of impaired glucose tolerance: evidence for impairment of incretin-induced insulin secretion. Diabetologia 2000; 43(7): 852-8.
[] [PMID: 10952457]
Zhang F, Tang X, Cao H, et al. Impaired secretion of total glucagon-like peptide-1 in people with impaired fasting glucose combined impaired glucose tolerance. Int J Med Sci 2012; 9(7): 574-81.
[] [PMID: 22991496]
Muscelli E, Mari A, Natali A, et al. Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab 2006; 291(6): E1144-50.
[] [PMID: 16478775]
Tura A, Muscelli E, Gastaldelli A, Ferrannini E, Mari A. Altered pattern of the incretin effect as assessed by modelling in individuals with glucose tolerance ranging from normal to diabetic. Diabetologia 2014; 57(6): 1199-203.
[] [PMID: 24658843]
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): 3717-23.
[] [PMID: 11502801]
Laakso M, Zilinskaite J, Hansen T, et al. EUGENE2 Consortium Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study Diabetologia. 2008; 51(3): 502-11.
[] [PMID: 18080106]
Færch K, Torekov SS, Vistisen D, et al. GLP-1 Response to Oral Glucose Is Reduced in Prediabetes, Screen-Detected Type 2 Diabetes, and Obesity and Influenced by Sex: The ADDITION-PRO Study. Diabetes 2015; 64(7): 2513-25.
[] [PMID: 25677912]
Shen J, Chen Z, Chen C, Zhu X, Han Y. Impact of incretin on early-phase insulin secretion and glucose excursion. Endocrine 2013; 44(2): 403-10.
[] [PMID: 23283820]
Nathanson D, Zethelius B, Berne C, Holst JJ, Sjöholm A, Nyström T. Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease. Diabetologia 2010; 53(2): 277-80.
[] [PMID: 19936703]
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): 668-77.
[] [PMID: 2676668]
Byrne MM, Gliem K, Wank U, et al. Glucagon-like peptide 1 improves the ability of the beta-cell to sense and respond to glucose in subjects with impaired glucose tolerance. Diabetes 1998; 47(8): 1259-65.
[] [PMID: 9703326]
Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012; 8(12): 728-42.
[] [PMID: 22945360]
Russell-Jones D. Molecular, pharmacological and clinical aspects of liraglutide, a once-daily human GLP-1 analogue. Mol Cell Endocrinol 2009; 297(1-2): 137-40.
[] [PMID: 19041364]
Knudsen LB. Liraglutide: the therapeutic promise from animal models. Int J Clin Pract Suppl 2010; (167): 4-11.
[] [PMID: 20887299]
Mehta A, Marso SP, Neeland IJ. Liraglutide for weight management: a critical review of the evidence. Obes Sci Pract 2017; 3(1): 3-14.
[] [PMID: 28392927]
Marso 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): 311-22.
[] [PMID: 27295427]
Xu X, Chen J, Hu L, et al. Liraglutide regulates the viability of pancreatic α-cells and pancreatic β-cells through cAMP-PKA signal pathway. Life Sci 2018; 195: 87-94.
[] [PMID: 29225111]
Tamura K, Minami K, Kudo M, Iemoto K, Takahashi H, Seino S. Liraglutide improves pancreatic Beta cell mass and function in alloxan-induced diabetic mice. PLoS One 2015; 10(5)e0126003
[] [PMID: 25938469]
Shimoda M, Kanda Y, Hamamoto S, et al. The human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes. Diabetologia 2011; 54(5): 1098-108.
[] [PMID: 21340625]
Shao Y, Yuan G, Feng Y, Zhang J, Guo X. Early liraglutide treatment is better in glucose control, β-cell function improvement and mass preservation in db/db mice. Peptides 2014; 52: 134-42.
[] [PMID: 24406898]
Kapodistria K, Tsilibary EP, Kotsopoulou E, Moustardas P, Kitsiou P. Liraglutide, a human glucagon-like peptide-1 analogue, stimulates AKT-dependent survival signalling and inhibits pancreatic β-cell apoptosis. J Cell Mol Med 2018; 22(6): 2970-80.
[] [PMID: 29524296]
Bregenholt S, Møldrup A, Blume N, et al. The long-acting glucagon-like peptide-1 analogue, liraglutide, inhibits beta-cell apoptosis in vitro. Biochem Biophys Res Commun 2005; 330(2): 577-84.
[] [PMID: 15796922]
Wang K, Sun Y, Lin P, et al. Liraglutide Activates AMPK Signaling and Partially Restores Normal Circadian Rhythm and Insulin Secretion in Pancreatic Islets in Diabetic Mice. Biol Pharm Bull 2015; 38(8): 1142-9.
[] [PMID: 26040899]
Dejgaard HF, Frandsenf CS, Kielgast URD, et al. 59-OR: Liraglutide Preserved Insulin Secretion in Adults with Newly Diagnosed Type 1 Diabetes: The New Lira Trial. Diabetes 2019; 61((Supplement 1))
Kramer CK, Zinman B, Choi H, Connelly PW, Retnakaran R. Chronic liraglutide therapy induces an enhanced endogenous glucagon-like peptide-1 secretory response in early type 2 diabetes. Diabetes Obes Metab 2017; 19(5): 744-8.
[] [PMID: 28181363]
DeFronzo RA, Abdul-Ghani MA. Preservation of β-cell function: the key to diabetes prevention. J Clin Endocrinol Metab 2011; 96(8): 2354-66.
[] [PMID: 21697254]
Wajchenberg BL. Clinical approaches to preserve beta-cell function in diabetes. Adv Exp Med Biol 2010; 654: 515-35.
[] [PMID: 20217513]
Mudaliar S. Choice of early treatment regimen and impact on β-cell preservation in type 2 diabetes. Int J Clin Pract 2013; 67(9): 876-87.
[] [PMID: 23952467]
Guo N, Sun J, Chen H, Zhang H, Zhang Z, Cai D. Liraglutide prevents diabetes progression in prediabetic OLETF rats. Endocr J 2013; 60(1): 15-28.
[] [PMID: 22986487]
Moran TH, Bi S. Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: developmental aspects. Dev Psychobiol 2006; 48(5): 360-7.
[] [PMID: 16770763]
Cummings BP, Stanhope KL, Graham JL, et al. Chronic administration of the glucagon-like peptide-1 analog, liraglutide, delays the onset of diabetes and lowers triglycerides in UCD-T2DM rats. Diabetes 2010; 59(10): 2653-61.
[] [PMID: 20622169]
Cummings BP, Digitale EK, Stanhope KL, et al. Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat. Am J Physiol Regul Integr Comp Physiol 2008; 295(6): R1782-93.
[] [PMID: 18832086]
Sturis J, Gotfredsen CF, Rømer J, et al. GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on beta-cell mass dynamics. Br J Pharmacol 2003; 140(1): 123-32.
[] [PMID: 12967942]
Luo X, Pan L, Nie A, et al. Liraglutide protects pancreatic beta cells during an early intervention in Gato-Kakizaki rats. J Diabetes 2013; 5(4): 421-8.
[] [PMID: 23590680]
Zheng J, Chen T, Zhu Y, et al. Liraglutide prevents fast weight gain and β-cell dysfunction in male catch-up growth rats. Exp Biol Med (Maywood) 2015; 240(9): 1165-76.
[] [PMID: 25710926]
Gao M, Deng XL, Liu ZH, et al. Liraglutide protects β-cell function by reversing histone modification of Pdx-1 proximal promoter in catch-up growth male rats. J Diabetes Complications 2018; 32(11): 985-94.
[] [PMID: 30177467]
Toots M, Seppa K, Jagomäe T, et al. Preventive treatment with liraglutide protects against development of glucose intolerance in a rat model of Wolfram syndrome. Sci Rep 2018; 8(1): 10183.
[] [PMID: 29976929]
Plaas M, Seppa K, Reimets R, et al. Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration. Sci Rep 2017; 7(1): 10220.
[] [PMID: 28860598]
Streckel E, Braun-Reichhart C, Herbach N, et al. Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition. J Transl Med 2015; 13: 73.
[] [PMID: 25890210]
Hanley NA, Hanley KP, Miettinen PJ, Otonkoski T. Weighing up beta-cell mass in mice and humans: self-renewal, progenitors or stem cells? Mol Cell Endocrinol 2008; 288(1-2): 79-85.
[] [PMID: 18450368]
Astrup A, Rössner S, Van Gaal L, et al. NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomized, double-blind, placebo-controlled study. Lancet 2009; 374: 1606-16.
[] [PMID: 19853906]
Astrup A, Carraro R, Finer N, et al. NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide Int J Obes. 2012; 36(6): 843-54.
[] [PMID: 21844879]
Kim SH, Abbasi F, Lamendola C, et al. Benefits of liraglutide treatment in overweight and obese older individuals with prediabetes. Diabetes Care 2013; 36(10): 3276-82.
[] [PMID: 23835684]
Kim SH, Liu A, Ariel D, et al. Pancreatic beta cell function following liraglutide-augmented weight loss in individuals with prediabetes: analysis of a randomised, placebo-controlled study. Diabetologia 2014; 57(3): 455-62.
[] [PMID: 24326527]
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): 380-6.
[] [PMID: 12540611]
Ariel D, Kim SH, Abbasi F, Lamendola CA, Liu A, Reaven GM. Effect of liraglutide administration and a calorie-restricted diet on lipoprotein profile in overweight/obese persons with prediabetes. Nutr Metab Cardiovasc Dis 2014; 24(12): 1317-22.
[] [PMID: 25280957]
Pi-Sunyer X, Astrup A, Fujioka K, et al. SCALE Obesity and Prediabetes NN8022-1839 Study Group. A Randomized, Controlled Trial of 30 mg of Liraglutide in Weight Management N Engl J Med. 2015; 373(1): 11-22.
[] [PMID: 26132939]
le Roux CW, Astrup A, Fujioka K, et al. SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial Lancet. 2017; 389(10077): 1399-409.
[] [PMID: 28237263]
Fujioka K, O’Neil PM, Davies M, et al. Early Weight Loss with Liraglutide 3.0 mg Predicts 1-Year Weight Loss and is Associated with Improvements in Clinical Markers. Obesity (Silver Spring) 2016; 24(11): 2278-88.
[] [PMID: 27804269]
Lau D, Fujioka K, Greenway F, et al. Early weight loss responders to liraglutide 3mg had greater weight loss, regression to normoglycemia and reduced type 2 diabetes development at 3 years vs. early non responders: Scale Obesity and Prediabetes. Can J Diabetes 2016; 40: S33.
Santilli F, Simeone PG, Guagnano MT, et al. Effects of Liraglutide on Weight Loss, Fat Distribution, and β-Cell Function in Obese Subjects With Prediabetes or Early Type 2 Diabetes. Diabetes Care 2017; 40(11): 1556-64.
[] [PMID: 28912305]
Larsen JR, Vedtofte L, Jakobsen MSL, et al. Effect of Liraglutide Treatment on Prediabetes and Overweight or Obesity in Clozapine- or Olanzapine-Treated Patients With Schizophrenia Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry 2017; 74(7): 719-28.
[] [PMID: 28601891]
Larsen JR, Svensson CK, Vedtofte L, et al. High prevalence of prediabetes and metabolic abnormalities in overweight or obese schizophrenia patients treated with clozapine or olanzapine. CNS Spectr 2018; 1-12.
[PMID: 30596361]
Svensson CK, Larsen JR, Vedtofte L, et al. One-year follow-up on liraglutide treatment for prediabetes and overweight/obesity in clozapine- or olanzapine-treated patients. Acta Psychiatr Scand 2019; 139(1): 26-36.
[] [PMID: 30374965]
Capristo E, Panunzi S, De Gaetano A, et al. Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study. Diabetes Metab 2018; 44(3): 235-42.
[] [PMID: 29398254]
Pi-Sunyer X, Obesity SCALE. SCALE Obesity and Prediabetes Investigators. Liraglutide in Weight Management N Engl J Med. 2015; 373(18): 1781-2.
[PMID: 26510028]
Nexøe-Larsen CC, Sørensen PH, Hausner H, et al. Effects of liraglutide on gallbladder emptying: A randomized, placebo-controlled trial in adults with overweight or obesity. Diabetes Obes Metab 2018; 20(11): 2557-64.
[] [PMID: 29892986]
Eichholzer M, Huang DJ, Modlasiak A, et al. Impact of body mass index on prognostically relevant breast cancer tumor characteristics. Breast Care (Basel) 2013; 8(3): 192-8.
[] [PMID: 24415969]
Funch D, Mortimer K, Li L, et al. Is there an association between liraglutide use and female breast cancer in a real-world setting? Diabetes Metab Syndr Obes 2018; 11: 791-806.
[] [PMID: 30538516]
Hicks BM, Yin H, Yu OH, Pollak MN, Platt RW, Azoulay L. Glucagon-like peptide-1 analogues and risk of breast cancer in women with type 2 diabetes: population based cohort study using the UK Clinical Practice Research Datalink. BMJ 2016; 355: i5340.
[PMID: 27797785]
Pyke C, Heller RS, Kirk RK, et al. GLP-1 receptor localization in monkey and human tissue: novel distribution revealed with extensively validated monoclonal antibody. Endocrinology 2014; 155(4): 1280-90.
[] [PMID: 24467746]
Kumarathurai P, Anholm C, Larsen BS, et al. Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study. Diabetes Care 2017; 40(1): 117-24.
[] [PMID: 27797930]
Egan AG, Blind E, Dunder K, et al. Pancreatic safety of incretin-based drugs--FDA and EMA assessment. N Engl J Med 2014; 370(9): 794-7.
[] [PMID: 24571751]
Chadwick KD, Fletcher AM, Parrula MC, et al. Occurrence of spontaneous pancreatic lesions in normal and diabetic rats: a potential confounding factor in the nonclinical assessment of GLP-1-based therapies. Diabetes 2014; 63(4): 1303-14.
[] [PMID: 24222349]
Steinberg WM, Rosenstock J, Wadden TA, Donsmark M, Jensen CB, DeVries JH. Impact of Liraglutide on Amylase, Lipase, and Acute Pancreatitis in Participants With Overweight/Obesity and Normoglycemia, Prediabetes, or Type 2 Diabetes: Secondary Analyses of Pooled Data From the SCALE Clinical Development Program. Diabetes Care 2017; 40(7): 839-48.
[] [PMID: 28473337]
Steinberg WM, Nauck MA, Zinman B, et al. LEADER Trial investigators LEADER 3--lipase and amylase activity in subjects with type 2 diabetes: baseline data from over 9000 subjects in the LEADER Trial Pancreas. 2014; 43(8): 1223-31.
[] [PMID: 25275271]
Drucker DJ. Mechanisms of action and therapeutic application of glucagon like peptide-1. Cell Metab 2018; 27(4): 740-56.
[] [PMID: 29617641]
Bjerre Knudsen L, Madsen LW, Andersen S, et al. Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology 2010; 151(4): 1473-86.
[] [PMID: 20203154]
Madsen LW, Knauf JA, Gotfredsen C, et al. GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology 2012; 153(3): 1538-47.
[] [PMID: 22234463]
Rosol TJ. On-target effects of GLP-1 receptor agonists on thyroid C-cells in rats and mice. Toxicol Pathol 2013; 41(2): 303-9.
[] [PMID: 23471186]
Hegedüs L, Moses AC, Zdravkovic M, Le Thi T, Daniels GH. GLP-1 and calcitonin concentration in humans: lack of evidence of calcitonin release from sequential screening in over 5000 subjects with type 2 diabetes or nondiabetic obese subjects treated with the human GLP-1 analog, liraglutide. J Clin Endocrinol Metab 2011; 96(3): 853-60.
[] [PMID: 21209033]
Hegedüs L, Sherman SI, Tuttle RM, et al. LEADER Publication Committee on behalf of the LEADER Trial Investigators. No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial Diabetes Care. 2018; 41(3): 620-2.
[] [PMID: 29279300]
Nauck MA, Jensen TJ, Rosenkilde C, Calanna S, Buse JB. LEADER Publication Committee on behalf of the LEADER Trial Investigators. Neoplasms Reported With Liraglutide or Placebo in People With Type 2 Diabetes: Results From the LEADER Randomized Trial Diabetes Care. 2018; 41(8): 1663-71.
[] [PMID: 29898902]
Azoulay L, Filion KB, Platt RW, et al. Canadian Network for Observational Drug Effect Studies Investigators. Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study BMJ. 2016; 352: i581.
[] [PMID: 26888382]
Bethel MA, Patel RA, Merrill P, et al. EXSCEL Study Group. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis Lancet Diabetes Endocrinol. 2018; 6(2): 105-3.
[] [PMID: 29221659]
Drucker DJ. The Ascending GLP-1 Road From Clinical Safety to Reduction of Cardiovascular Complications. Diabetes 2018; 67(9): 1710-9.
[] [PMID: 30135132]
Uusitupa M, Lindström J, Tuomilehto J. Prevention of type 2 diabetes-success story that is waiting for next steps. Eur J Clin Nutr 2018; 72(9): 1260-6.
[] [PMID: 30185842]
Retnakaran R. Joe Doupe lecture: emerging strategies for the preservation of pancreatic beta-cell function in early type 2 diabetes. Clin Invest Med 2014; 37(6): E414-20.
[] [PMID: 25618275]
Kitabchi AE, Temprosa M, Knowler WC, et al. Diabetes Prevention Program Research Group. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin Diabetes. 2005; 54(8): 2404-14.
[] [PMID: 16046308]
Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin N Engl J Med. 2002; 346(6): 393-403.
[] [PMID: 11832527]
Retnakaran R, Kramer CK, Choi H, Swaminathan B, Zinman B. Liraglutide and the preservation of pancreatic β-cell function in early type 2 diabetes: the LIBRA trial. Diabetes Care 2014; 37(12): 3270-8.
[] [PMID: 25249651]
Tran S, Kramer CK, Zinman B, Choi H, Retnakaran R. Effect of chronic liraglutide therapy and its withdrawal on time to postchallenge peak glucose in type 2 diabetes. Am J Physiol Endocrinol Metab 2018; 314(3): E287-95.
[] [PMID: 29183873]
Bunck MC, Diamant M, Cornér A, et al. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care 2009; 32(5): 762-8.
[] [PMID: 19196887]
Bunck MC, Cornér A, Eliasson B, et al. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care 2011; 34(9): 2041-7.
[] [PMID: 21868779]
RISE Consortium Restoring Insulin Secretion (RISE): design of studies of β-cell preservation in prediabetes and early type 2 diabetes across the life span Diabetes Care. 2014; 37(3): 780-8.
[] [PMID: 24194506]
Reid TS. Practical use of glucagon-like- peptide-1 receptor agonists therapy in primary care. Clin Diabetes 2013; 31: 148-57.
Whitten JS. Liraglutide (Saxenda) for Weight Loss. Am Fam Physician 2016; 94(2): 161-6.
[PMID: 27419334]
Hunt B, Vega-Hernandez G, Valentine WJ, Kragh N. Evaluation of the long-term cost-effectiveness of liraglutide vs lixisenatide for treatment of type 2 diabetes mellitus in the UK setting. Diabetes Obes Metab 2017; 19(6): 842-9.
[] [PMID: 28124820]
Shah D, Risebrough NA, Perdrizet J, Iyer NN, Gamble C, Dang-Tan T. Cost-effectiveness and budget impact of liraglutide in type 2 diabetes patients with elevated cardiovascular risk: a US-managed care perspective. Clinicoecon Outcomes Res 2018; 10: 791-803.
[] [PMID: 30532570]
Murphy CF, Docherty NG, le Roux CW. Liraglutide: another reason to target prediabetes? Oncotarget 2017; 8(59): 99203-4.
[] [PMID: 29245886]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [699 - 715]
Pages: 17
DOI: 10.2174/1573399816666191230113446
Price: $65

Article Metrics

PDF: 40