Obesity is recognised as an important risk factor for type 2 diabetes, inducing insulin resistance and pancreatic beta-cell dysfunction. These obesity-related defects tend to progress following weight gain and can eventually lead to worsening hyperglycaemia over time. Thus, effective weight management is crucial for glycaemic control in overweight and obese patients with type 2 diabetes. Current standard strategies for weight management in these patients include lifestyle interventions and pharmacotherapy. Bariatric surgery has become a promising new option for the treatment of obese patients with type 2 diabetes and in recent years incretin-based therapies have become available, which exhibit favourable effects on body weight. Herein, the efficacy of available weight loss interventions is assessed and the role of newer antidiabetic agents examined, focusing on incretin-based therapies.
SmythSHeronA.Diabetes and obesity: The twin epidemics. Nat Med2006;12:75–80.
4.
NorrisSLZhangXAvenellALong-term non-pharmacologic weight loss interventions for adults with type 2 diabetes. Cochrane Database Syst Rev2005;2:CD004095.
5.
AstrupAFinerN.Redefining type 2 diabetes: ‘diabesity’ or ‘obesity dependent diabetes mellitus’? Obes Rev2000;1:57–9.
6.
KleinSAllisonDBHeymsfieldSBWaist circumference and cardiometabolic risk: A consensus statement from shaping America's health: Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Diabetes Care2007;30:1647–52.
7.
LeeCMHuxleyRRWildmanRPWoodwardM.Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI: A meta-analysis. J Clin Epidemiol2008;61:646–53.
8.
DeFronzoRAPathogenesis of type 2 diabetes mellitus. Med Clin North Am2004;88:787–835.
9.
KleinSSheardNFPi SunyerXWeight management through lifestyle modification for the prevention and management of type 2 diabetes: Rationale and strategies: A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care2004;27:2067–73.
10.
TuomilehtoJLindströmJErikssonJGFinnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med2001;344:1343–50.
11.
KnowlerWCFowlerSEHammanRFDiabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet2009;374:1677–86.
12.
LinaresLloret CGreenfieldJRCzernichowS.Effect of weight-reducing agents on glycaemic parameters and progression to type 2 diabetes: A review. Diabet Med2008;25:1142–50.
13.
WingRRMarcusMDEpsteinLHSalataR.Type II diabetic subjects lose less weight than their overweight nondiabetic spouses. Diabetes Care1987;10:563–6.
14.
Pi SunyerFXWeight loss in type 2 diabetic patients. Diabetes Care2005;28:1526–7.
15.
MaloneM.Medications associated with weight gain. Ann Pharmacother2005;39:2046–55.
16.
GoldsteinDJBeneficial health effects of modest weight loss. Int J Obes Relat Metab Disord1992;16:397–415.
17.
WingRRKoeskeREpsteinLHLong-term effects of modest weight loss in type II diabetic patients. Arch Intern Med1987;147:1749–53.
18.
National Institute for Clinical Excellence. Obesity: the prevention, identification, assessment and management of overweight and obesity in adults and children (Guideline CG43). London: NICE, 2006. www.nice.org.uk/nicemedia/pdf/CG43NICEGuideline.pdf. Accessed April 2010.
19.
Central Office of Information for the Department of Health. Care pathway for the management of overweight and obesity. London: Department of Health, 2006. www.dh.gov.uk/assetRoot/04/13/45/60/04134560.pdf. Accessed April 2010.
20.
TsigosCHainerVBasdevantAManagement of obesity in adults: European clinical practice guidelines. Obes Facts2008;1:106–16.
21.
National Institute for Clinical Excellence. Type 2 diabetes. National clinical guideline for management in primary and secondary care (update). (Guideline CG66). London: NICE, 2008. www.nice.org.uk/nicemedia/pdf/CG66FullGuideline0509.pdf. Accessed April 2010.
22.
NathanDMBuseJBDavidsonMBMedical management of hyperglycaemia in type 2 diabetes mellitus: A consensus algorithm for the initiation and adjustment of therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia2009;52:17–30.
23.
BrownSAUpchurchSAndingRPromoting weight loss in type II diabetes. Diabetes Care1996;19:613–24.
24.
DelahantyLMNathanDMImplications of the diabetes prevention program and Look AHEAD clinical trials for lifestyle interventions. J Am Diet Assoc2008;108(4 suppl 1):S66–72.
25.
Look AHEAD Research Group. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes. One-year results of the Look AHEAD trial. Diabetes Care2007;30:1374–83.
26.
TurnerRCCullCAFrighiVHolmanRR, for the UKPDS Group. Glycemic control with diets, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus. JAMA1999;281:2005–12.
European Medicines Agency (EMA). European Medicines Agency recommends suspension of marketing authorisations for sibutramine: Weight-loss medicine associated with increased risk of cardiovascular events to be removed from all markets in the European Union. Press release 21 Jan 2010. www.ema.europa.eu/pdfs/human/referral/sibutramine/3940810en.pdf. Accessed April 2010.
29.
PadwalRKezouhALevineMEtminanM.Long-term persistence with orlistat and sibutramine in a population-based cohort. Int J Obes (Lond)2007;31:1567–70.
30.
RubinoFKaplanLMSchauerPRCummingsDE, on behalf of the Diabetes Surgery Summit Delegates. The diabetes surgery summit consensus conference: Recommendations for the evaluation and use of gastrointestinal surgery to treat type 2 diabetes mellitus. Ann Surg2010;251:399–405.
31.
MisraAChowbeyPMakkarBMConcensus Group. Consensus statement for diagnosis of obesity, abdominal obesity and the metabolic syndrome for Asian Indians and recommendations for physical activity, medical and surgical management. J Assoc Physicians India2009;57:163–70.
32.
FlattPRDayCBaileyCJBariatric surgery: To treat diabesity. Br J Diabetes Vasc Dis2009;9:103–7.
33.
CannonCPKumarA.Treatment of overweight and obesity: Lifestyle, pharmacologic, and surgical options. Clin Cornerstone2009;9:55–71.
34.
PinkneyJ.Bariatric surgery for diabetes: Gastric banding is simple and safe. Br J Diabetes Vasc Dis2010;10:139–42.
35.
BuchwaldHEstokRFahrbachKWeight and type 2 diabetes after bariatric surgery: Systematic review and meta-analysis. Am J Med2009;122:248–56.
36.
SjöstromLNarbroKSjöstromCDEffects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med2007;357:741–52.
37.
KnopFKResolution of type 2 diabetes following gastric bypass surgery: Involvement of gut-derived glucagon and glucagonotropic signalling. Diabetologia2009;52:2270–6.
38.
PoriesWJBariatric surgery: Risks and rewards. J Clin Endocrinol Metab2008;93:S89–S96.
39.
BrethauerSAChandBSchauerPRRisks and benefits of bariatric surgery: Current evidence. Cleve Clin J Med2006;73:993–1007.
40.
BultMJFVan DalenTMullerAFSurgical treatment of obesity. Eur J Endocrin2008;158:135–45.
41.
SalemLJensenCCFlumDRAre bariatric surgical outcomes worth their cost? A systematic review. J Am Coll Surg2005;200:270–8.
42.
BaggioLLDruckerDJBiology of incretins: GLP-1 and GIP. Gastroenterology2007;132:2131–57.
43.
NauckMABallerBMeierJJGastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes. Diabetes2004;53(suppl 3):S190–6.
44.
HolstJJThe physiology of glucagon-like peptide 1. Physiol Rev2007; 87:1409–39.
AstrupARössnerSVan GaalL, On behalf of the NN8022–1807 Study Group. Effects of liraglutide in the treatment of obesity: A randomised, double-blind, placebo-controlled study. Lancet2009;374:1606–16.
SchwarzBGouveiaMChenJCost-effectiveness of sitagliptin-based treatment regimens in European patients with type 2 diabetes and haemoglobin A1c above target on metformin monotherapy. Diabetes Obes Metab2008;10(suppl 1):43–55.
53.
SullivanSDCristanchoAlfonso RConnerCA simulation of the comparative long-term effectiveness of liraglutide and glimepiride monotherapies in patients with type 2 diabetes mellitus. Pharmacotherapy2009;29:1280–8.
54.
KhooJRaynerCKJonesKLHorowitzM.Incretin-based therapies: New treatments for type 2 diabetes in the new millennium. Ther Clin Risk Manag2009;5:683–98.
55.
ChenYEDruckerDJTissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem1997;272:4108–15.
56.
BuseJBHenryRRHanJEffects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care2004;27:2628–35.
57.
DeFronzoRARatnerREHanJEffects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care2005;28:1092–100.
58.
KendallDMRiddleMCRosenstockJEffects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care2005;28:1083–91.
59.
ZinmanBHoogwerfBJDuránGSThe effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: A randomized trial. Ann Intern Med2007;146:477–85.
60.
National Institute for Clinical Excellence. Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes (Guideline CG87). London: NICE, 2009. http://guidance.nice.org.uk/CG87/Guidance/pdf/English. Accessed April 2010.
61.
KlonoffDCBuseJBNielsenLLExenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin2008;24:275–86.
62.
NauckMADuranSKimDA comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: A non-inferiority study. Diabetologia2007;50:259–67.
63.
AmoriRELauJPittasAGEfficacy and safety of incretin therapy in type 2 diabetes: Systematic review and meta-analysis. JAMA2007;298:194–206.
64.
GarberAHenryRRatnerRLiraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): A randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet2009;373:473–81.
65.
ZinmanBGerichJBuseJBEfficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care2009;32:1224–30.
66.
BuseJBRosenstockJSestiGLiraglutide once a day versus exenatide twice a day for type 2 diabetes: A 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet2009; 374:39–47.
67.
JonesRussell DVaagASchmitzOLiraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): A randomised controlled trial. Diabetologia2009;52:2046–55.
68.
MarreMShawJBrandleMLiraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabet Med2009;26:268–78.
69.
JendleJNauckMAMatthewsDRWeight 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 Metab2009; 11:1163–72.
70.
NauckMFridAHermansenKEfficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes: The LEAD (liraglutide effect and action in diabetes)-2 study. Diabetes Care2009;32:84–90.
71.
MatthewsDMarreMThiLe TLiraglutide, a once-daily human GLP-1 analog, significantly improves β-cell function in subjects with type 2 diabetes. Diabetes2008;57(suppl 1): A1 50 (505-P).
72.
PratleyRENauckMBaileyTFor the 1860-LIRA-DPP-4-Study Group. Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: A 26-week, randomised, parallel-group, open-label trial. Lancet2010; 375:1447–56.
73.
ParksMRosebraughC.Weighing risks and benefits of liraglutide: The FDA's review of a new antidiabetic therapy. N Engl J Med2010;362: 774–7.
74.
AndersonSLTrujilloJMAssociation of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother2010;44:904–9.
75.
RosenstockJBrazgRAndryukPJEfficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing pioglitazone therapy in patients with type 2 diabetes: A 24-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther2006;28:1556–68.
76.
AschnerPKipnesMSLuncefordJKEffect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care2006;29:2632–7.
77.
GoldsteinBJFeinglosMNLuncefordJKEffect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care2007;30:1979–87.
78.
HermansenKKipnesMLuoEEfficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab2007;9:733–45.
79.
NauckMAMeiningerGShengDEfficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, compared with the sulfonylurea, glipizide, in patients with type 2 diabetes inadequately controlled on metformin alone: A randomized, double-blind, non-inferiority trial. Diabetes Obes Metab2007;9:194–205.
80.
VilsbøllTRosenstockJJärvinenYki HEfficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab2010;12:167–77.
81.
BosiECamisascaRPColloberCEffects of vildagliptin on glucose control over 24 weeks in patients with type 2 diabetes inadequately controlled with metformin. Diabetes Care2007;30:890–5.
82.
GarberAJFoleyJEBanerjiMAEffects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea. Diabetes Obes Metab2008;10:1047–56.
83.
GarberAJSchweizerABaronMAVildagliptin in combination with pioglitazone improves glycaemic control in patients with type 2 diabetes failing thiazolidinedione monotherapy: A randomized, placebo-controlled study. Diabetes Obes Metab2007;9:166–74.
84.
BolliGDottaFRochotteECohenSEEfficacy and tolerability of vildagliptin vs. pioglitazone when added to metformin: A 24-week, randomized, double-blind study. Diabetes Obes Metab2008;10:82–90.
85.
RichterBEchtlerBandeira EBergerhoffKLerchCLDipeptidyl pepti-dase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev2008;2:CD006739.
