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Objective Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis. Measurements A linear regression equation [HbA1c (%) = 0.0164 × FPG (mg/dL) + 4.2] was derived using the screening cohort (n = 6829) and applied to calculate predicted HbA1c. This was subtracted from the observed HbA1c to determine HGI in the baseline cohort with 2hPG data (n = 3945). Baseline variables plus prediabetes and diabetes diagnosis by FPG, HbA1c, and 2hPG were compared among low, moderate, and high HGI subgroups. Results The proportion of women and Black/African American individuals increased from low to high HGI subgroups. Mean FPG decreased and mean HbA1c increased from low to high HGI subgroups, consistent with the HGI calculation; however, mean 2hPG was not significantly different among HGI subgroups. Conclusions High HGI was associated with Black race and female sex as reported previously. The observation that 2hPG was not different across HGI subgroups suggests that variation in postprandial glucose is not a significant source of population variation in HGI. Exclusive use of HbA1c for diagnosis will classify more Black individuals and women as having prediabetes compared with using FPG or 2hPG.

Context Intermediate-term glycemic control metrics fulfill a need for measures beyond hemoglobin A1C. Objective Compare glycated albumin (GA), a 14-day blood glucose measure, with other glycemic indices. Design 24-week prospective study of assay performance. Setting 8 US clinics. Participants Subjects with type 1 (n = 73) and type 2 diabetes (n = 77) undergoing changes to improve glycemic control (n = 98) or with stable diabetes therapy (n = 52). Interventions GA, fructosamine, and A1C measured at prespecified intervals. Mean blood glucose (MBG) calculated using weekly self-monitored blood glucose profiles. Main Outcome Measures Primary: Pearson correlation between GA and fructosamine. Secondary: magnitude (Spearman correlation) and direction (Kendall correlation) of change of glycemic indices in the first 3 months after a change in diabetes management. Results GA was more concordant (60.8%) with changes in MBG than fructosamine (55.5%) or A1C (45.5%). Across all subjects and visits, the GA Pearson correlation with fructosamine was 0.920. Pearson correlations with A1C were 0.655 for GA and 0.515 for fructosamine (P < .001) and with MBG were 0.590 and 0.454, respectively (P < .001). At the individual subject level, Pearson correlations with both A1C and MBG were higher for GA than for fructosamine in 56% of subjects; only 4% of subjects had higher fructosamine correlations with A1C and MBG. GA had a higher Pearson correlation with A1C and MBG in 82% and 70% of subjects, respectively. Conclusions Compared with fructosamine, GA correlates significantly better with both short-term MBG and long-term A1C and may be more useful than fructosamine in clinical situations requiring monitoring of intermediate-term glycemic control (NCT02489773).

The global PIONEER program investigated the efficacy and safety of oral semaglutide, a glucagon-like peptide-1 receptor agonist. Patients with type 2 diabetes were randomized to once-daily oral semaglutide (3, 7 or 14 mg, or flexibly dosed [flex]), placebo, or active comparator (empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg). This exploratory subgroup analysis evaluated the effect of race on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of treatment (week 26, 52 or 78). Data were analyzed from PIONEER 1-5, 7 and 8 by race (White, Asian, Black/African American). Baseline characteristics were generally similar across subgroups except for BW, which was lower in Asian patients. Generally, greater HbA1c reductions were observed with oral semaglutide 14 mg/flex vs. comparators across subgroups (Table). In PIONEER 1, 4 and 8, there was a significant interaction between treatment and race, with greater HbA1c reductions and estimated treatment differences in Asian patients than in other subgroups (Table). Overall, BW reductions were greater for oral semaglutide vs. comparators, regardless of subgroup and without significant interactions between treatment and race. Our findings in this exploratory subgroup analysis suggest that, in some PIONEER trials, Asian patients achieve greater HbA1c reductions than other race groups when treated with oral semaglutide. Disclosure C. Desouza: Consultant; Self; AstraZeneca, Bayer AG, Novo Nordisk A/S. A. Amod: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi-Aventis, Servier. Consultant; Self; Servier. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Novo Nordisk A/S, Sanofi-Aventis, Servier. K. Kallenbach: None. P.J. Lin: Speaker’s Bureau; Self; Abbott, AstraZeneca, Bausch + Lomb, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Mead Johnson Nutrition, Merck & Co., Inc., Novo Nordisk Inc., Sun Pharmaceutical Industries Ltd. Other Relationship; Self; Elsevier. M. Abildlund Nielsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. R. Sørrig: Employee; Self; Novo Nordisk A/S. E. Montanya: Advisory Panel; Self; Sanofi. Consultant; Self; Novartis Pharmaceuticals Corporation. Employee; Spouse/Partner; Almirall. Speaker’s Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Funding Novo Nordisk A/S

OBJECTIVE To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA1c 7.0–10.0% (53–86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA1c from baseline to week 26. RESULTS In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA1c was observed with semaglutide from −1.1% (0.05 mg) to −1.9% (0.3 mg) and with liraglutide from −0.5% (0.3 mg) to −1.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was −0.02% (P < 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8–54.0% and 21.9–41.5% of patients, respectively. CONCLUSIONS Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA1c compared with liraglutide or placebo but with a higher frequency of GI AEs.

Aim: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects. Materials and methods: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol-specified composite endpoint was the proportion of participants achieving HbA1c

AIMS: The Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) trial is a randomized clinical trial comparing glycemic effects of four diabetes medications added to metformin in type 2 diabetes (T2D). Microvascular and macrovascular diseases are secondary outcomes. We evaluated the prevalence and risk factor relationships for microvascular and macrovascular complications in the GRADE cohort at study entry. METHODS: Complication prevalence and risk factors were analyzed based on data from screening in all consenting participants meeting GRADE eligibility. Logistic regression and Z-statistics were used to assess risk factor relationships with complications. RESULTS: We enrolled 5047 T2D participants [mean age 57 years; 36% female; mean knownT2D duration 4 years (all

Aims Both fasting (FPG) and postprandial plasma glucose (PPG) contribute to HbA1c levels. We investigated the relationship between achievement of American Diabetes Association (ADA) and American Association of Clinical Endocrinologists (AACE) recommended FPG and/or PPG targets and glycaemic efficacy outcomes in two trials. Methods In this post hoc analysis, data from participants with Type 2 diabetes in the phase 3 LixiLan‐O (NCT 02058147) and LixiLan‐L (NCT 02058160) trials were evaluated to compare the relationship between achievement of society‐recommended FPG and/or PPG targets and efficacy (HbA1c change, HbA1c goal attainment, weight change) and safety outcomes in the treatment groups. Results Across treatment arms, iGlarLixi achieved the highest proportion of participants meeting both ADA‐ and AACE‐recommended FPG and PPG targets at study end in both trials. A higher proportion of participants in the iGlarLixi (fixed‐ratio combination of insulin glargine and lixisenatide) vs. insulin glargine alone or lixisenatide alone treatment arms achieved HbA1c goals (P, What's new? Achievement of both fasting (FPG) and postprandial plasma glucose (PPG) targets is important for optimal glycaemic control in Type 2 diabetes.This post hoc analysis of the LixiLan‐O and LixiLan‐L trials shows that targeting both FPG and PPG results in improved glycaemic control, with weight neutrality and a low risk of hypoglycaemia.It is clinically desirable to achieve control of FPG and PPG. More people treated with iGlarLixi achieved control, and those who did so reached an HbA1c target of

Background: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. Methods: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30–59 mL/min per 1·73 m2, and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA1c (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. Findings: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA1c (estimated mean change of −1·0 percentage point (SE 0·1; −11 mmol/mol [SE 0·8]) vs −0·2 percentage points (SE 0·1; −2 mmol/mol [SE 0·8]); estimated treatment difference [ETD]: −0·8 percentage points, 95% CI −1·0 to −0·6; p1c −1·1 percentage points (SE 0·1; −12 mmol/mol [SE 0·8] versus −0·1 percentage points (SE 0·1; −1 mmol/mol [SE 0·8]; ETD −1·0 percentage points, 95% CI −1·2 to −0·8; p

We previously reported that fish oil in combination with cyclooxygenase (COX) inhibitors exerts enhanced hypolipidemic and anti-inflammatory effects in mice. Here, we sought to determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in combination with naproxen (NX), a COX inhibitor, on dyslipidemia and gene expression in adipose tissue (AT) in humans. Obese dyslipidemic patients were randomly assigned to one of these interventions for 12 wk: 1) Standard nutrition counseling (control), 2) ω-3 PUFAs (2 g twice daily), 3) NX (220 mg twice daily), and 4) ω-3 PUFAs (2 g twice daily) + NX (220 mg twice daily). The serum triglycerides showed a trend towards a reduction and a significant reduction (P0.05) in ω-3 and ω3 + NX-treated subjects, respectively, compared to control. The mRNA expression of vascular cell adhesion molecule-1 (Vcam1), an inflammatory marker, increased significantly in AT of ω-3 PUFA-treated subjects but not in ω-3 PUFAs+NX-treated group. The plasma level of glycine-conjugated hyodeoxycholic acid, a secondary bile acid with hypolipidemic property, increased significantly in ω-3 PUFAs + NX-treated group. Our data suggest that combining NX with ω-3 PUFAs increases their effectiveness in reducing serum TG and favorably altering AT gene expression and plasma bile acid profile.

Patients (pts) with T2D and renal impairment have limited glucose-lowering treatment options. Oral semaglutide (sema) 14 mg once daily (N=163) was compared with placebo (pbo, N=161) in a 26-week, randomized, phase 3a trial (NCT02827708) in pts with T2D and moderate renal impairment (eGFR 30-59 mL/min/1.73 m2), receiving 1-2 glucose-lowering agents (could include basal insulin). Endpoints: change in HbA1c (primary) and body weight (BW, secondary) to week 26. Two estimands were defined: treatment policy (regardless of trial product discontinuation or rescue medication) and trial product (on trial product without rescue medication) in all randomized pts. Oral sema was superior to (treatment policy) and significantly better than (trial product) pbo in reducing HbA1c and BW (Table). More pts reached HbA1c, BW loss, and composite targets with oral sema. At follow-up, eGFR was unchanged. Fewer pts on oral sema required rescue medication (4 vs. 10%). Adverse events were more frequent with oral sema (74 vs. 65%), most often mild/moderate nausea (19 vs. 7%). More patients on oral sema prematurely discontinued trial product (15 vs. 5%), mainly due to nausea and vomiting. In conclusion, in pts with T2D and moderate renal impairment, oral sema provided superior glycemic control and BW loss compared to pbo at 26 weeks, did not appear to affect renal function, and was well tolerated in line with the population and GLP-1RA class. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. S. Rosenlund: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.W. Eriksson: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Zealand Pharma A/S. Consultant; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. R.E. Pratley: Consultant; Self; Sanofi US. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Janssen Global Services, LLC., Janssen Research & Development, Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk Inc., Pfizer Inc., Sanofi, Takeda Development Center Americas, Inc. T. Sathyapalan: Speaker's Bureau; Self; Novo Nordisk Foundation. Other Relationship; Self; Bristol-Myers Squibb Company, Eli Lilly and Company, Sanofi-Aventis. T.M. Blicher: Employee; Self; Novo Nordisk A/S. O.H. Hels: Employee; Self; Novo Nordisk A/S. C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi US. Funding Novo Nordisk A/S

In recent years, Cardiovascular Outcome Event Trials (CVOTs) in type 2 diabetes mellitus (T2DM) have demonstrated that sodium glucose transporter 2 inhibitors (SGLT2i) could reduce major adverse cardiovascular events (MACE) and cardiovascular mortality independent of a glucose lowering mechanism. SGLT2i trials reported significant results that have generated biologically plausible theories with regard to the macrovascular benefit. In this review, we have summarized and discussed the results of the CANVAS program. The CANVAS program is unique as it is an analysis of two aggregated cohorts. The two cohorts were similar at baseline but had different durations of exposure to canagliflozin. It showed a 14% reduction in the primary MACE composite. However, the individual components of the MACE composite were not significantly different from placebo. Initial analysis also indicated a reno-protective effect. The results of the CANVAS program are similar overall yet different when compared to the EMPA-REG OUTCOMES trial, especially with regard to cardiovascular mortality and adverse event profile. This could possibly be due to the differences in the cardiovascular risk profile of the enrolled population in the two trials. Other possibilities include drug-specific effects and different mechanisms of lowering overall MACE. In addition, a brief comparison of CANVAS to the CVD-REAL indicates that the CANVAS trial results may apply to a larger, more generalized population than those in the CANVAS program.

This study assessed the relationship between FPG, PPG and glycated hemoglobin (A1C) target attainment using ADA glycemic targets in patients (pts) with T2D. A post-hoc analysis of the phase 3 LixiLan-O (NCT02058147) trial assessed the efficacy and safety of iGlarLixi (n=468) vs. insulin glargine U100 (iGlar) (n=466) and lixisenatide (Lixi) (n=233) in pts uncontrolled on metformin ± a second OAD, continuing only on metformin, over a 30-week period. The proportion of pts reaching both FPG and PPG target was highest for iGlarLixi, while the proportions of those reaching FPG or PPG targets only were highest for iGlar (targeting FPG) and Lixi (targeting PPG), respectively (Figure 1A). There was a stepwise trend in A1C change, end-of-study A1C, and proportion of pts reaching A1C goals in favor of iGlarLixi, followed by iGlar and Lixi (Figure 1B-D). Pts reaching both FPG and PPG targets had the greatest A1C drop and lowest A1C values, and represented the largest proportion of pts acheiving A1C target. No differences were observed in hypoglycemia rates in all treatment arms, and a greater proportion of pts experienced weight loss with iGlarLixi vs. iGlar (55.3% vs. 39.9%). By simultaneously targeting fasting and postprandial hyperglycemia, iGlarLixi treatment results in greater A1C reduction and better A1C target attainment than iGlar or Lixi alone. Disclosure C. Desouza: Consultant; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Medscape. V. Fonseca: Consultant; Self; Abbott. Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Eli Lilly and Company. Stock/Shareholder; Self; Amgen Inc.. Consultant; Self; Asahi Kasei Corporation, AstraZeneca, Novo Nordisk Inc., ADOCIA, Intarcia Therapeutics, Inc., Sanofi-Aventis. J.P. Frias: Research Support; Self; AbbVie Inc., Allergan, Amgen Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company. Consultant; Self; CeQur Corporation. Research Support; Self; Cirius Therapeutics, AstraZeneca, Calibra Medical, Elcelyx Therapeutics, Inc.. Consultant; Self; Elcelyx Therapeutics, Inc.. Research Support; Self; Eli Lilly and Company, Genentech, Inc., Ionis Pharmaceuticals, Inc., ICON plc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Johnson & Johnson Diabetes Institute, LLC.. Research Support; Self; Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc.. Consultant; Self; Ligand Pharmaceuticals, Inc.. Research Support; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc., Sanofi. Consultant; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Theracos, Inc. L. Van Gaal: Advisory Panel; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Speaker's Bureau; Self; Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen J & J, Merck MSD, Novo Nordisk, Sanofi and Servier/Intarcia. Research Support; Self; EU (Hepadip & Resolve consortium) and National Research Funds. F. Giorgino: Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH. Research Support; Self; Eli Lilly and Company, Johnson & Johnson Services, Inc.. Consultant; Self; MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care Health and Digital Solutions, Sanofi. Research Support; Self; Takeda Development Centre Europe Ltd.. J. Chao: None. T.A. Dex: Employee; Self; Sanofi US. Stock/Shareholder; Self; Pfizer Inc., Merck Sharp & Dohme Corp., Teva Pharmaceutical Industries Ltd.. M. Roberts: None. A. Saremi: Employee; Self; Sanofi US. L.A. Leiter: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Research Support; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Merck & Co., Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Servier. Speaker's Bureau; Self; Servier. Research Support; Self; Servier. Advisory Panel; Self; Amgen Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Amgen Inc., Esperion Therapeutics, Kowa Pharmaceuticals America, Inc., The Medicines Company. Advisory Panel; Self; Akcea Therapeutics, Novartis Pharmaceuticals Corporation.

Obesity disproportionately affects rural residents in the United States, and primary care has the potential to fill a major gap in the provision of weight management services for rural communities. The objective of this cluster-randomized pragmatic trial is to evaluate the comparative effectiveness of three obesity treatment models in rural primary care: the Intensive Behavior Therapy fee-for-service (FFS) model reimbursed by Medicare, a team-based model that recognizes the patient-centered medical home (PCMH) as a preferred delivery approach, and the centralized disease management (DM) model, in which phone-based counseling is provided outside of the primary care practice. We hypothesize that the PCMH and DM treatments will be more effective than FFS in reducing weight at 24 months. Thirty-six practices from the rural Midwestern U.S. are randomized to deliver one of the three interventions to 40 patients (N=1440) age 20 to 75 with a BMI 30-45 kg/m(2). In the FFS arm, primary care providers and their personnel counsel patients to follow evidence-based weight loss guidelines using the Medicare-designated treatment schedule. In the PCMH arm, patients receive a comprehensive weight management intervention delivered locally by practice personnel using a combination of in-person and phone-based group sessions. In the DM arm, the same intervention is delivered remotely by obesity treatment specialists via group conference calls. The primary outcome is weight loss at 24 months. Additional measures include fasting glucose, lipids, quality of life indicators, and implementation process measures. Findings will illuminate effective obesity treatment intervention(s) in rural primary care.