OBESITY IN TYPE 2 DIABETES

Transcription

1 OBESITY IN TYPE 2 DIABETES Ashley Crowl, PharmD, BCACP Assistant Professor University of Kansas Objectives Review how to manage obesity in patients with type-2 diabetes mellitus Compare antiobesity agents and differentiate benefits vs. risks Obesity 34.9% of adults and 16.9% of youth are obese 23% of these patients have type 2 diabetes mellitus (T2DM) Estimated annual medical costs =$147 billion related to obesity Medical costs = $1,429 more for obese patients than those of normal weight Arthritis DM CVD Obesity Mortality Cancer 1. Ogden, et al. JAMA Obesity management. AHA/ACC/TOS Finkelstein, et al. Health Affairs

2 Managing Obesity Pt needs to lose weight if BMI 30 or BMI 25 with additional risk factor Assess readiness to make lifestyle changes [take into account competing priorities (i.e. uncontrolled DM or HTN)] Initial weight loss goal of 5-10% of baseline weight within 6 months. Decrease by 500 kcal/day. Manage other risk factors Management of Obesity.AHA/ACC/TOS Obesity Tx: Antiobesity Agents Insulin Resistance Tx: Metformin T2DM Tx: Anti-diabetes medications Goswami G. J Clin Med Patient Case CG 41 yo WM I just can t get rid of this tire around my waist PMH: T2DM, hyperlipidemia, tobacco abuse, GERD BP: 116/70 mmhg HR: 80 bpm BMI: 30.5 BMP: WNL LDL: 103 AST/ALT: 23/19 A1C= 10.3% Medications: Atorvastatin 40 HS Lantus 20 u HS Lisinopril 2.5 mg Qday Metformin 1000 mg BID Attempted 3 months of lifestyle changes, achieved 5% weight loss 2

3 Metformin Weight neutral vs. weight loss ~2-3 kg weight loss Reduces all-cause mortality, stroke and diabetes-related endpoints Goswami G. J Clin Med UKPDS 34. Lancet Next step after Metformin? Weight Gain Sulfonylureas (+2-3 kg) Thiazolidinediones (+2-4 kg) Insulin (+2-5 kg) Weight Neutral/ Loss GLP1 analogs ( kg) DPP4-inhibitors (0-1.5 kg) Amylin analogs (-2.5 kg) SGLT2 inhibitors (-2-3 kg) Goswami G. J Clin Med Next step after Metformin? GLP-1 agonists SGLT2-inhibitors 3

4 Change in Weight (Kg) Exenatide BID Liraglutide Exenatide BID Exenatide QW Exenatide QW Liraglutide Albiglutide Liraglutide Dulaglutide Liraglutide GLP-1 vs. Basal Insulin Trial Design Pop. Tx groups A1c (%) P Value Wt (kg) P Value Lead-5, Russell- Jones et al. Duration -3, Diamant et al. N= 581 (Met ± SU) N=456 (Met ± SU) 26 wk, openlabel Liraglutide placebo -0.24% < glargine < year, openlabel Exenatide <0.001 glargine GLP-1 vs. Basal Insulin GLP-1 Basal A1C reduction ~1-1.9% Any goal based on titration Effect on body weight CV effects Simplicity Weight loss Limited data, but suggest favorable ( BP) Standard dose, limited monitoring Weight gain No effect Dose titration, SMBG Side effects Nausea, vomiting hypoglycemia Gallwitz B. Diabetes Care GLP1 Comparative Weight Loss Chart Title LEAD-6 DURATION-5 DURATION-6 HARMONY-7 AWARD Exenatide BID Exenatide QW Liraglutide Albiglutide Dulaglutide Trujillo, et al. Ther Adv Endocrinol Metab Feb;6(1):

5 GLP-1 s with Basal Insulin Meta-analysis of 15 studies examined efficacy and safety of combination Achievement of the ideal trifecta? Glycemic control, no hypoglycemia, no weight gain Eng,et al. Lancet Dec 20;384(9961): GLP-1 s with Basal Insulin Primary Endpoints Reduction in A1c (%) vs. any treatment Reduction in weight (kg) vs. any treatment Proportion achieving A1c <7% vs. any treatment Incidence of hypoglycemia vs. any treatment Weighted mean difference (95% CI) Relative Risk (95% CI) (-0.60 to -0.29) (-4.90 to -1.54) ( ) 0.99 ( ) Eng,et al. Lancet Dec 20;384(9961): GLP-1 and Insulin Try GLP-1 before Basal if A1C <9.5% Try GLP-1 + Basal before adding prandial Less weight gain Less hypoglycemia Similar (some better) A1C control Gallwitz B. Diabetes Care

6 GLP1 s in general Liraglutide Best A1C and weight reduction Weekly GLP1 s Least GI side effects May increase adherence Trujillo J. Ther Adv Endrocrinol Metab SGLT2-Inhibitors Trial Design Pop Tx groups A1c (%) P Value Wt (Kg) P Value Ridderst rale et al. Lancet yr, dbl blind, RCT N= 1545 Empagliflozin (25 mg/d) Glimepiride (2.71 mg/d) < < Schernt haner et al. Diabetes Care wk, openlabel N= 755 (Met +SU) Canagliflozin (300 mg/d) Sitagliptin (100 mg/d) < < SGLT2-Inhibitors Use caution! FDA issued warning May 2015: Canagliflozin, dapagliflozin and empagliflozin may lead to ketoacidosis Adverse Event Reporting System identified 20 cases of acidosis from March June 2014 Triggers: major illness reduced fluids reduced insulin dose FDA safety communication. Accessed Aug

7 Patient Case CG 41 yo WM I just can t get rid of this tire around my waist PMH: T2DM, hyperlipidemia, tobacco abuse, GERD BP: 116/70 mmhg HR: 80 bpm BMI: 30.5 BMP: WNL LDL: 103, TG: 128 AST/ALT: 23/19 A1C= 10.3% Medications: Atorvastatin 40 HS Lantus 20 u HS Lisinopril 2.5 mg Qday Metformin 1000 mg BID Attempted 3 months of lifestyle changes, achieved 5% weight loss What do you recommend? ANTIOBESITY AGENTS Managing Obesity Pt needs to lose weight if BMI 30 or BMI 25 with additional risk factor Assess readiness to make lifestyle changes [take into account competing priorities (i.e. uncontrolled DM or HTN)] Initial weight loss goal of 5-10% of baseline weight within 6 months. Decrease by 500 kcal/day. Manage other risk factors Management of Obesity.AHA/ACC/TOS

8 Managing Obesity Start comprehensive lifestyle interventions alone or with adjunctive therapies Consider antiobesity agents after initial lifestyle changes with BMI 30 or BMI 27 with additional co-morbidity Continue medication if 5% weight loss within 12 weeks, d/c if not. Refer for more intensive behavioral treatment or bariatric surgery. Management of Obesity.AHA/ACC/TOS Obesity= chronic disease Maximum weight loss achieved at 6 months Lifestyle or medications Maintenance treatment Continue long-term ( 2 years) comprehensive weight loss programs Monthly contact Reduced-calorie diet Physical activity (>200 min/week) Pharmacotherapy (studies up to 2 years) Management of Obesity.AHA/ACC/TOS Antiobesity comparison chart Orlistat Lorcaserin Phen/Top Bup/Nalt Liraglutide Dose 120 mg 10 mg 3.75 mg/ 23 mg-15 mg/92 mg 90 mg/ 8mg- 300 mg/ 32 mg mg Freq. TID BID daily BID daily Cost $16/d $8/d $8/d $8/d $40/d ADE Efficacy + + (NNT=4) +++ (NNT=2) ++ (NNT=3) +++ (NNT=2) 8

9 Choosing an agent Lorcaserin Moderate efficacy, low side effects Caution (avoid) use with serotonergic agents Phentermine/topiramate High efficacy, high side effects Avoid use in moderate-severe CV risk Bupropion/naltrexone Moderate efficacy, high side effects Avoid use with opioids, avoid use in seizures Lorcaserin Safety Smith et al. BLOOM. NEJM 2010 Phentermine Safety Jordan J. J Hypertension

10 Patient Case KH 52 yo WM PMH: DM, HTN, HLD, MI, Obesity, Tobacco Abuse BP: 122/80 mmhg, HR 76 BMI 56 A1C= 7.1% LDL:97, TG 115 AST/ALT: 16/20 BMP: WNL Medications: Aspirin 81 mg daily Bupropion 150 mg XR BID Lisinopril 20 mg daily Metoprolol 25 mg daily Nitrostat 0.4 mg SL PRN Omega 3 Fatty acids- 1 daily Atorvastatin 40 mg HS What would you recommend to manage his obesity? Surgery Bariatric Surgery compared to medications for T2DM with BMI >35 DM remission occurred in 75% in gastric bypass & 95% in biliopancreatic-diversion A1C reductions: 7.69±0.57% (medications) 6.35±1.42% (gastric bypass) 4.95±0.49% (biliopancreatic-diversion) Mingrone et al. NEJM Summary Start with lifestyle changes This needs to be ingrained! Obesity with T2DM Manage DM first Use weight neutral/loss meds metformin + GLP-1 s are ideal SGLT2 s can be considered but watch for ADE 10

11 Summary Add antiobesity agents Most studies only looked at yo, BMI Avoid bupropion/naltrexone with opioids Avoid phentermine/topiramate in moderate-high CV risk Caution with lorcaserin and other serotonin agents Must stop if < 5% of weight-loss from baseline is not achieved in 3 months Individualize treatment! Resources for patients: htm QUESTIONS? Ashley Crowl, PharmD, BCACP ANCROWL@KU.EDU 11