Weight change after initiation of oral hypoglycemic monotherapy for diabetes predicts 5-year mortality: An observational study.
ABSTRACT: PURPOSE:To investigate whether weight change in the first year after initiating an oral hypoglycemic agent (OHA) for type 2 diabetes treatment is associated with mortality in a national cohort. PROCEDURES:We prospectively followed Veterans Health Administration patients with type 2 diabetes initiating treatment with an OHA and not receiving any other diabetes pharmacotherapy for at least one year. Information on OHAs, weight, co-morbidities, other medications, demographics, and laboratory measurements was obtained from electronic medical records. Logistic regression was used to estimate 5-year mortality odds by weight change during the first year after OHA treatment initiation. FINDINGS:Patients (mean age 65years, 97% male, mean BMI 32.3kg/m2) initiating OHA monotherapy between 2003 and 2008 totaled 145,198 (metformin n=89,111, glipizide n=27,100, glyburide n=25,226, rosiglitazone n=3,761). Most patients (65%) maintained a stable weight (change ?5% from baseline) during the first year after OHA initiation. Those losing >5% of baseline weight had a significantly higher odds of death over the subsequent 5-years ranging from 1.64 to 2.13 depending on OHA type. In the metformin group, weight gain >5% of baseline was also associated with higher odds of 5-year mortality. The same results were obtained after conducting three sensitivity analyses that excluded patients for the following reasons: weight loss in the one year prior to OHA initiation, weight change >100lbs, or weight change >50lbs. CONCLUSIONS:Weight loss was associated with higher odds of 5-year mortality among patients initiating an OHA, as was weight gain for metformin only.
Project description:The purpose of this study was to describe the prescription pattern of initial treatment for type 2 diabetes (T2DM) in Beijing from 2011 to 2015.We selected 790,339 newly diagnosed outpatients with T2DM from the Beijing Medical Claim Data for Employees database between January 2011 and December 2015. The percentages of different treatments and agents were calculated from the patients' 1st prescriptions. Subgroup analyses were conducted for primary, secondary, and tertiary hospital settings.The initial treatments given to 57.7%, 30.7%, and 11.7% of patients were oral hypoglycemic agent (OHA) monotherapy, OHA polytherapy, and insulin, respectively. Alpha-glucosidase inhibitors (AGIs) (43.0%) were the most commonly used agents for monotherapy, followed by metformin (35.5%) and sulfonylureas (14.9%). AGIs were most commonly used in primary hospitals (52.0%), while metformin was prescribed most often in secondary (37.6%) and tertiary (41.8%) hospitals. From 2011 to 2015, there were increases in the use of AGIs (40.1-41.1%, P?<?.001) and metformin (34.0-40.4%, P?<?.001), but a decrease in the use of sulfonylureas (18.1-12.8%, P?<?.001). Similar trends were seen in the different hospital settings. Metformin plus an AGI, a sulfonylurea plus an AGI, and metformin plus a sulfonylurea were the most common OHA polytherapy combinations. The use of metformin plus an AGI increased from 13.8% in 2011 to 19.7% in 2015 (P?<?.001), while the use of a sulfonylurea plus an AGI, and metformin plus a sulfonylurea, did not change significantly.Half of newly diagnosed patients with T2DM received an initial treatment of OHA monotherapy. Although the use of metformin increased from 2011 to 2015, both AGIs and metformin were the most commonly prescribed agents. The patterns differed from those of most other countries and identification of the underlying reasons will require further investigation.
Project description:Background:The benefits of sodium glucose cotransporters 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus include plasma glucose control, reduction in body weight and blood pressure, and low risk of hypoglycemia, although they may also cause genitourinary infections, polyuria, or volume depletion. It is not clear whether dapagliflozin, an SGLT2 inhibitor, improves treatment satisfaction among patients in a comprehensive way despite the negative side effects. This study assessed the effect of dapagliflozin on glycosylated hemoglobin (HbA1c), body weight, and treatment satisfaction in overweight patients with type 2 diabetes mellitus treated with oral hypoglycemic agents. Methods:This multicenter, open-label, single-arm observational study included patients with type 2 diabetes mellitus administering dapagliflozin 5 or 10 mg per day for 14 weeks. Changes in treatment satisfaction were evaluated using a new version of the Oral Hypoglycemic Agent-Questionnaire (OHA-Q ver. 2) consisting of 23 items. Correlation between treatment satisfaction and HbA1c levels and body weight were analyzed using the Spearman's rank-correlation coefficient. Results:Of the 221 patients enrolled, 188 completed the study. Mean HbA1c decreased from 7.8 ± 0.7% (62.1 ± 7.5 mmol/mol) to 7.3 ± 0.8% (55.9 ± 8.7 mmol/mol) (change - 0.6 ± 0.7%, P < 0.001) and body weight decreased from 82.5 ± 14.6 to 80.7 ± 14.8 kg (change - 2.3 ± 2.8 kg, P < 0.001). OHA-Q ver. 2 was validated as well, the mean OHA-Q ver. 2 total score increased from 44.3 ± 9.4 to 46.6 ± 9.8 (best score 69, worst score 0; change 2.3 ± 6.6, P < 0.001). The change in body weight significantly correlated with the OHA-Q ver. 2 total score (Spearman's ? = - 0.17, P = 0.035). The change in HbA1c levels significantly correlated with the satisfaction subscale score (Spearman's ? = - 0.19, P = 0.011). Conclusions:Dapagliflozin significantly improved treatment satisfaction among patients with type 2 diabetes mellitus for 14 weeks. Body weight loss significantly correlated with treatment satisfaction.Trial registration UMIN-CTR: UMIN000016304.
Project description:INTRODUCTION:Weight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naïve PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS:Adult, treatment-naïve PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with >10% weight gain at two and five years. RESULTS:Among 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of >10% body weight increase at two years (adjusted odds ratio = 1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI). CONCLUSIONS:PWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.
Project description:AIMS:Sulfonylureas are recommended as second-line treatment in the management of type 2 diabetes. However, they are still commonly used also as first-line treatment instead of metformin. Given the controversial cardiovascular safety of sulfonylureas, we aimed to determine if their use as first-line treatment is associated with adverse cardiovascular events among patients with newly treated type 2 diabetes compared with metformin. METHODS:We conducted a population-based cohort study of patients with newly treated type 2 diabetes using the UK's Clinical Practice Research Datalink. Initiators of metformin and sulfonylurea monotherapy were matched on high-dimensional propensity score, and Cox proportional hazards models were used to compare the rate of cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular death, and all-cause mortality) with sulfonylureas vs metformin. RESULTS:Our cohort included 94 750 patients initiating treatment for type 2 diabetes, 17 612 on a sulfonylurea and 77 138 on metformin. After matching, sulfonylurea monotherapy, compared with metformin monotherapy, was not associated with an increased risk of myocardial infarction (hazard ratio [HR]: 1.04, 95% confidence interval [CI]: 0.85-1.25) but was associated with increased risks of ischaemic stroke (HR: 1.25, 95% CI: 1.002-1.56), cardiovascular death (HR: 1.25, 95% CI: 1.06-1.47), and all-cause mortality (HR: 1.60, 95% CI: 1.45-1.76). This represents an additional 2.0 ischaemic strokes, 3.5 cardiovascular deaths, and 21.4 all-cause deaths per 1,000 patients per year with sulfonylureas. CONCLUSIONS:Initiating treatment of type 2 diabetes with a sulfonylurea rather than metformin is associated with higher rates of ischaemic stroke, cardiovascular death, and all-cause mortality.
Project description:Metformin produced weight loss and delayed or prevented diabetes in the Diabetes Prevention Program (DPP). We examined its long-term safety and tolerability along with weight loss, and change in waist circumference during the DPP and its long-term follow-up.The randomized double-blind clinical trial of metformin or placebo followed by a 7-8-year open-label extension and analysis of adverse events, tolerability, and the effect of adherence on change in weight and waist circumference.No significant safety issues were identified. Gastrointestinal symptoms were more common in metformin than placebo participants and declined over time. During the DPP, average hemoglobin and hematocrit levels were slightly lower in the metformin group than in the placebo group. Decreases in hemoglobin and hematocrit in the metformin group occurred during the first year following randomization, with no further changes observed over time. During the DPP, metformin participants had reduced body weight and waist circumference compared with placebo (weight by 2.06 ± 5.65% vs. 0.02 ± 5.52%, P < 0.001, and waist circumference by 2.13 ± 7.06 cm vs. 0.79 ± 6.54 cm, P < 0.001 in metformin vs. placebo, respectively). The magnitude of weight loss during the 2-year double-blind period was directly related to adherence (P < 0.001). Throughout the unblinded follow-up, weight loss remained significantly greater in the metformin group than in the placebo group (2.0 vs. 0.2%, P < 0.001), and this was related to the degree of continuing metformin adherence (P < 0.001).Metformin used for diabetes prevention is safe and well tolerated. Weight loss is related to adherence to metformin and is durable for at least 10 years of treatment.
Project description:OBJECTIVES:To evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme. DESIGN:DISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019. SETTING:Primary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations. PARTICIPANTS:A total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy. PRIMARY AND SECONDARY OUTCOME MEASURES:The proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change. RESULTS:Of the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (?75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe. CONCLUSIONS:A substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes. TRIAL REGISTRATION NUMBERS:NCT02322762 and NCT02226822.
Project description:<h4>Background & aims</h4>It remains limited whether diabetes mellitus (DM) and hypertension (HTN) affect the prognosis of advanced hepatocellular carcinoma (HCC) treated with sorafenib. Our study attempted to elucidate the roles of DM/HTN and the effects of diabetes medications among advanced HCC patients receiving sorafenib.<h4>Methods</h4>From August 2012 to February 2018, 733 advanced HCC patients receiving sorafenib were enrolled at China Medical University, Taichung, Taiwan. According to the presence/absence of DM or HTN, they were divided into four groups: control [DM(-)/HTN(-), n = 353], DM-only [DM(+)/HTN(-), n = 91], HTN-only [DM(-)/HTN(+), n = 184] and DM+HTN groups [DM(+)/HTN(+), n = 105]. Based on the types of diabetes medications, there were three groups among DM patients (the combined cohort of DM-only and DM+HTN groups), including metformin (n = 63), non-metformin oral hypoglycemic agent (OHA) (n = 104) and regular insulin (RI)/neutral protamine hagedorn (NPH) groups (n = 29). We then assessed the survival differences between these groups.<h4>Results</h4>DM-only and DM+HTN groups significantly presented longer overall survival (OS) than control group (control vs. DM-only, 7.70 vs. 11.83 months, p = 0.003; control vs. DM+HTN, 7.70 vs. 11.43 months, p = 0.008). However, there was no significant OS difference between control and HTN-only group (7.70 vs. 8.80 months, p = 0.111). Besides, all groups of DM patients showed significantly longer OS than control group (control vs. metformin, 7.70 vs. 12.60 months, p = 0.011; control vs. non-metformin OHA, 7.70 vs. 10.80 months, p = 0.016; control vs. RI/NPH, 7.70 vs. 15.20 months, p = 0.026).<h4>Conclusions</h4>Rather than HTN, DM predicts better prognosis in advanced HCC treated with sorafenib. Besides, metformin, non-metformin OHA and RI/NPH are associated with longer survival among DM-related advanced HCC patients receiving sorafenib.
Project description:AIM:To describe population-level time trends in prescribing patterns of type 2 diabetes therapy, and in short-term clinical outcomes (glycated haemoglobin [HbA1c], weight, blood pressure, hypoglycaemia and treatment discontinuation) after initiating new therapy. MATERIALS AND METHODS:We studied 81 532 people with type 2 diabetes initiating a first- to fourth-line drug in primary care between 2010 and 2017 inclusive in United Kingdom electronic health records (Clinical Practice Research Datalink). Trends in new prescriptions and subsequent 6- and 12-month adjusted changes in glycaemic response (reduction in HbA1c), weight, blood pressure and rates of hypoglycaemia and treatment discontinuation were examined. RESULTS:Use of dipeptidyl peptidase-4 inhibitors as second-line therapy near doubled (41% of new prescriptions in 2017 vs. 22% in 2010), replacing sulphonylureas as the most common second-line drug (29% in 2017 vs. 53% in 2010). Sodium-glucose co-transporter-2 inhibitors, introduced in 2013, comprised 17% of new first- to fourth-line prescriptions by 2017. First-line use of metformin remained stable (91% of new prescriptions in 2017 vs. 91% in 2010). Over the study period there was little change in average glycaemic response and in the proportion of people discontinuing treatment. There was a modest reduction in weight after initiating second- and third-line therapy (improvement in weight change 2017 vs. 2010 for second-line therapy: -1.5 kg, 95% confidence interval [CI] -1.9, -1.1; P < 0.001), and a slight reduction in systolic blood pressure after initiating first-, second- and third-line therapy (improvement in systolic blood pressure change 2017 vs. 2010 range: -1.7 to -2.1 mmHg; all P < 0.001). Hypoglycaemia rates decreased over time with second-line therapy (incidence rate ratio 0.94 per year, 95% CI 0.88, 1.00; P = 0.04), mirroring the decline in use of sulphonylureas. CONCLUSIONS:Recent changes in prescribing of therapy for people with type 2 diabetes have not led to a change in glycaemic response and have resulted in modest improvements in other population-level short-term clinical outcomes.
Project description:<h4>Background</h4> We evaluated whether diet quality is a predictor of weight loss and reduced diabetes risk, independent of caloric intake in the Diabetes Prevention Program (DPP) cohort, a randomized clinical trial of adults at risk for diabetes. <h4>Methods</h4> This secondary analysis included 2914 participants with available data (964 intensive lifestyle (ILS), 977 metformin, 973 placebo). Dietary intake was assessed using a 117-item food frequency questionnaire. Diet quality was quantified using the Alternative Healthy Eating Index 2010 (AHEI). AHEI ranges from 0 to 110, with higher scores corresponding to higher quality diets. ILS participants had greater improvement (p?<?0.001) in AHEI over 1-year (4.2?±?9.0) compared to metformin (1.2?±?8.5) and placebo (1.4?±?8.4). We examined the association between AHEI change and weight change from baseline to 1-year using linear regression, and that between 1-year AHEI change and incident diabetes, using hazard models over an average 3?years follow-up. Models were evaluated within treatment group and adjusted for relevant characteristics including caloric intake, physical activity, BMI and AHEI. Models testing incident diabetes were further adjusted for baseline fasting and 2?h glucose. <h4>Results</h4> An increase in AHEI score was associated with weight loss in ILS [? per 10-point increase (SE) -1.2?kg (0.3, p?<?0.001)], metformin [??0. 90?kg (0.2, p?<?0.001)] and placebo [??0.55?kg (0.2, p?=?0.01)]. However, AHEI change was not associated with incident diabetes in any group before or after adjustment for weight change. <h4>Conclusions</h4> Controlling for weight, diet quality was not associated with diabetes incidence but helps achieve weight loss, an important factor in diabetes prevention. <h4>Supplementary Information</h4> The online version contains supplementary material available at 10.1186/s40795-020-00400-4.
Project description:AIM:To investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes. MATERIALS AND METHODS:We conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged ?18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within-drug yearly change in body weight after receiving add-on therapy with individual SUs during 5 years of follow-up. The secondary outcome was within-drug yearly change in glycated haemoglobin (HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration. RESULTS:A total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add-on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after. CONCLUSIONS:In patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add-on therapy to metformin, without the offset of relevant weight changes.