scholarly journals Metformin Reduces the Risk of Diverticula of Intestine in Taiwanese Patients with Type 2 Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Chin-Hsiao Tseng
Keyword(s):  
Incidence Rate ◽  
Lower Risk ◽  
Cox Regression ◽  
Age Groups ◽  
Confounding By Indication ◽  
Hazard Ratios ◽  
Cumulative Duration ◽  
Insurance Database

Aim: To investigate the risk of diverticula of intestine associated with metformin use.Methods: This retrospective cohort study used the Taiwan’s National Health Insurance database to enroll 307,548 ever users and 18,839 never users of metformin. The patients were followed up starting on January 1, 2006 and ending on a date up to December 31, 2011. To address confounding by indication, hazard ratios were derived from Cox regression based on the inverse probability of treatment weighting using propensity score.Results: During follow-up, newly diagnosed cases of diverticula were identified in 1,828 ever users (incidence rate: 125.59 per 100,000 person-years) and 223 never users (incidence rate: 268.17 per 100,000 person-years). Ever users had an approximately 54% lower risk, as shown by the overall hazard ratio of 0.464 (95% confidence interval 0.404–0.534). While patients categorized in each tertile of cumulative duration of metformin therapy were compared to never users, a dose-response pattern was observed with hazard ratios of 0.847 (0.730–0.983), 0.455 (0.391–0.531) and 0.216 (0.183–0.255) for the first (<27.37 months), second (27.37–59.70 months) and third (>59.70 months) tertiles, respectively. The findings were similar when the diagnosis of diverticula was restricted to the small intestine or to the colon. Subgroup analyses suggested that the lower risk of diverticula of intestine associated with metformin use was significant in all age groups of <50, 50–64 and ≥65 years, but the magnitude of risk reduction attenuated with increasing age.Conclusion: Metformin treatment is associated with a significantly reduced risk of diverticula of intestine.

Abstract MP05: Leisure-Time Running and Incident Type 2 Diabetes

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duck-chul Lee ◽  
Carl J. Lavie ◽  
Timothy S. Church ◽  
Xuemei Sui ◽  
Steven N. Blair
Keyword(s):  
Type 2 Diabetes ◽  
Lower Risk ◽  
Leisure Time ◽  
Cox Regression ◽  
Smoking Status ◽  
Physical Activities ◽  
Incident Type ◽  
Incident Type 2 Diabetes

Introduction: There is still little evidence on the dose-response relation between leisure-time running and incident type 2 diabetes (T2D). Hypothesis: We examined the hypothesis that running reduces the risk of developing T2D. Methods: Participants were 19,347 adults aged 18 to 100 years (mean age, 44) who received an extensive preventive medical examination during 1974-2006 in the Aerobics Center Longitudinal Study. Participants were free of cardiovascular disease, cancer, and T2D at baseline. Running and other physical activities were assessed on the medical history questionnaire by self-reported leisure-time activities during the past 3 months. We defined T2D as fasting glucose ≥126 mg/dl, insulin use, or physician-diagnosis during follow-up medical examinations. Cox regression was used to quantify the association between running and T2D after adjusting for baseline age, sex, examination year, body mass index, smoking status, heavy alcohol drinking, abnormal electrocardiogram, hypertension, hypercholesterolemia, and levels of other physical activities. Results: During an average follow-up of 6.5 years, 1,015 adults developed T2D. Approximately 30% of adults participated in leisure-time running. Runners had a 29% lower risk of developing T2D compared with non-runners. The hazard ratios (95% confidence intervals) of T2D were 0.97 (0.74-1.27), 0.66 (0.49-0.89), 0.62 (0.45-0.85), 0.78 (0.58-1.03), and 0.57 (0.42-0.79) across quintiles (Q) of running time (minutes/week); 0.99 (0.76-1.30), 0.60 (0.44-0.82), 0.72 (0.55-0.94), 0.65 (0.47-0.90), and 0.63 (0.47-0.86) across Q of running distance (miles/week); 1.08 (0.83-1.40), 0.67 (0.50-0.90), 0.70 (0.53-0.93), 0.61 (0.45-0.83), and 0.53 (0.36-0.76) across Q of running frequency (times/week); 0.95 (0.73-1.24), 0.70 (0.52-0.94), 0.62 (0.45-0.84), 0.73 (0.55-0.97), and 0.58 (0.42-0.80) across Q of total amount of running (MET-minutes/week); and 0.95 (0.71-1.28), 0.76 (0.59-0.99), 0.59 (0.42-0.83), 0.66 (0.51-0.85), and 0.62 (0.43-0.90) across Q of running speed (mph), respectively, compared with no running after adjusting for confounders including levels of other physical activities. Conclusions: Participating in leisure-time running is associated with markedly lower risk of developing T2D in adults. Except for those in the very lowest Q for running doses, even relatively low running doses (starting with Q 2) were associated with marked reductions in T2D risk over time, supporting the prescription of running to reduce T2D.

scholarly journals Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
You-Bin Lee ◽  
Kyungdo Han ◽  
Bongsung Kim ◽  
Seung-Eun Lee ◽  
Ji Eun Jun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Cox Regression ◽  
Early Mortality ◽  
Hazard Ratios ◽  
Epidemiological Characteristics

Abstract Background Both type 1 and type 2 diabetes are well-established risk factors for cardiovascular disease and early mortality. However, few studies have directly compared the hazards of cardiovascular outcomes and premature death among people with type 1 diabetes to those among people with type 2 diabetes and subjects without diabetes. Furthermore, information about the hazard of cardiovascular disease and early mortality among Asians with type 1 diabetes is sparse, although the clinical and epidemiological characteristics of Asians with type 1 diabetes are unlike those of Europeans. We estimated the hazard of myocardial infarction (MI), hospitalization for heart failure (HF), atrial fibrillation (AF), and mortality during follow-up in Korean adults with type 1 diabetes compared with those without diabetes and those with type 2 diabetes. Methods We used Korean National Health Insurance Service datasets of preventive health check-ups from 2009 to 2016 in this retrospective longitudinal study. The hazard ratios of MI, HF, AF, and mortality during follow-up were analyzed using the Cox regression analyses according to the presence and type of diabetes in ≥ 20-year-old individuals without baseline cardiovascular disease (N = 20,423,051). The presence and type of diabetes was determined based on the presence of type 1 or type 2 diabetes at baseline. Results During more than 93,300,000 person-years of follow-up, there were 116,649 MIs, 135,532 AF cases, 125,997 hospitalizations for HF, and 344,516 deaths. The fully-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MI, hospitalized HF, AF, and all-cause death within the mean follow-up of 4.6 years were higher in the type 1 diabetes group than the type 2 diabetes [HR (95% CI) 1.679 (1.490–1.893) for MI; 2.105 (1.901–2.330) for HF; 1.608 (1.411–1.833) for AF; 1.884 (1.762–2.013) for death] and non-diabetes groups [HR (95% CI) 2.411 (2.138–2.718) for MI; 3.024 (2.730–3.350) for HF; 1.748 (1.534–1.993) for AF; 2.874 (2.689–3.073) for death]. Conclusions In Korea, the presence of diabetes was associated with a higher hazard of cardiovascular disease and all-cause death. Specifically, people with type 1 diabetes had a higher hazard of cardiovascular disease and all-cause mortality compared to people with type 2 diabetes.

scholarly journals Mortality in Patients with Diabetic Foot Ulcers: Causes, Risk Factors, and Their Association with Evolution and Severity of Ulcer

2020 ◽  
Vol 9 (9) ◽  
pp. 3009
Author(s):  
José Antonio Rubio ◽  
Sara Jiménez ◽  
José Luis Lázaro-Martínez
Keyword(s):  
Diabetic Foot ◽  
Cox Regression ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
History Of

Background: This study reviews the mortality of patients with diabetic foot ulcers (DFU) from the first consultation with a Multidisciplinary Diabetic Foot Team (MDFT) and analyzes the main cause of death, as well as the relevant clinical factors associated with survival. Methods: Data of 338 consecutive patients referred to the MDFT center for a new DFU during the 2008–2014 period were analyzed. Follow-up: until death or until 30 April 2020, for up to 12.2 years. Results: Clinical characteristics: median age was 71 years, 92.9% had type 2 diabetes, and about 50% had micro-macrovascular complications. Ulcer characteristics: Wagner grade 1–2 (82.3%), ischemic (49.2%), and infected ulcers (56.2%). During follow-up, 201 patients died (59.5%), 110 (54.7%) due to cardiovascular disease. Kaplan—Meier curves estimated a reduction in survival of 60% with a 95% confidence interval (95% CI), (54.7–65.3) at 5 years. Cox regression analysis adjusted to a multivariate model showed the following associations with mortality, with hazard ratios (HRs) (95% CI): age, 1.07 (1.05–1.08); HbA1c value < 7% (53 mmol/mol), 1.43 (1.02–2.0); active smoking, 1.59 (1.02–2.47); ischemic heart or cerebrovascular disease, 1.55 (1.15–2.11); chronic kidney disease, 1.86 (1.37–2.53); and ulcer severity (SINBAD system) 1.12 (1.02–1.26). Conclusion: Patients with a history of DFU have high mortality. Two less known predictors of mortality were identified: HbA1c value < 7% (53 mmol/mol) and ulcer severity.

scholarly journals Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Neurology ◽  
2017 ◽  
Vol 89 (18) ◽  
pp. 1877-1885 ◽  
Author(s):  
Ariela R. Orkaby ◽  
Kelly Cho ◽  
Jean Cormack ◽  
David R. Gagnon ◽  
Jane A. Driver
Keyword(s):  
Lower Risk ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Confounding By Indication ◽  
Cox Proportional Hazards Models ◽  
Incident Dementia ◽  
Us Veterans

Objective:To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.Methods:This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.Results:We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61–0.73) and 0.78 (95% CI 0.72–0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79–0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87–1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99).Conclusions:After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

scholarly journals Metformin use is associated with a lower risk of uterine leiomyoma in female type 2 diabetes patients

2019 ◽  
Vol 10 ◽  
pp. 204201881989515 ◽  
Author(s):  
Chin-Hsiao Tseng
Keyword(s):  
Type 2 Diabetes ◽  
Lower Risk ◽  
Uterine Leiomyoma ◽  
Sensitivity Analyses ◽  
Matched Pair ◽  
Diagnostic Code ◽  
Hazard Ratios ◽  
Diabetes Patients

Background: Whether metformin may reduce the risk of uterine leiomyoma in type 2 diabetes patients has not been investigated. This retrospective cohort study compared the risk of uterine leiomyoma in ever versus never users of metformin. Methods: Female patients with new-onset type 2 diabetes during 1999–2005 were enrolled from the reimbursement database of Taiwan’s National Health Insurance and followed up from 1 January 2006 until 31 December 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort of 10,998 ever users and 10,998 never users of metformin. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the PS. Results: A total of 321 never users and 162 ever users developed uterine leiomyoma during follow up, with respective incidence of 704.65 and 329.82 per 100,000 person-years. The overall hazard ratio was 0.467 (95% confidence interval: 0.387–0.564). The hazard ratios for the first (<23.3 months), second (23.3–53.1 months), and third (>53.1 months) tertiles of cumulative duration were 0.881 (0.685–1.132), 0.485 (0.367–0.642), and 0.198 (0.134–0.291), respectively; and were 0.751 (0.576–0.980), 0.477 (0.360–0.632), and 0.277 (0.198–0.386), respectively, for the first (<655,000 mg), second 655,000–1,725,500 mg), and third (>1,725,500) tertiles of cumulative dose. Sensitivity analyses after excluding users of sulfonylurea, users of estrogen, users of insulin, users of incretin-based therapies during follow up, patients with irregular drug refills, patients who discontinued the use of metformin, patients who received metformin prescription less than four times, or redefining uterine leiomyoma by using ‘diagnostic code’ plus ‘procedure codes’ consistently supported a lower risk of uterine leiomyoma in ever users of metformin. Conclusion: Metformin use is associated with a lower risk of uterine leiomyoma.

Severe Hypoglycemia and Incident Heart Failure among Adults With Type 2 Diabetes

2021 ◽  
Author(s):  
Justin B Echouffo-Tcheugui ◽  
Arnaud D Kaze ◽  
Gregg C Fonarow ◽  
Sam Dagogo-Jack
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Relative Risk ◽  
Cox Regression ◽  
Severe Hypoglycemia ◽  
Medical Assistance ◽  
Hazard Ratios ◽  
Accord Study

Abstract Context The effect of severe hypoglycemia on the incidence of heart failure (HF) is unclear. Objective We evaluated the association of severe hypoglycemia with incident HF among individuals with type 2 diabetes. Methods We included participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. Severe hypoglycemia episodes were assessed during the initial 24 months following randomization and defined using two methods: symptomatic, severe hypoglycemic event requiring medical assistance (first definition) or requiring any assistance (second definition). Participants without HF at baseline and during the first 24 months of the study were prospectively followed for incident HF hospitalization. Multivariable Cox regression was used to generate adjusted hazard ratios (HR) for the association of severe hypoglycemia and incident HF. Results Among 9,208 participants (mean age 63 years, 38% female, 62% White), 365 had ≥ 1 episode of severe hypoglycemic. Over a median follow-up of 3 years, there were 249 incident HF events. After multivariable adjustment for relevant confounders, participants with severe hypoglycemia requiring medical assistance had a 68% higher relative risk of incident HF (HR 1.68, 95% CI 1.06-2.66), as compared to individuals who never experienced any episode of hypoglycemia. Severe hypoglycemia requiring any assistance was also associated with a 49% higher relative risk of HF (HR 1.49, 95% CI 1.01-2.21). Conclusion In a large cohort of adults with type 2 diabetes, severe hypoglycemia was independently associated with greater risk of incident HF.

scholarly journals Relationship between diabetic retinopathy stages and risk of major lower-extremity arterial disease in patients with type 2 diabetes

2020 ◽  
Author(s):  
Ninon Foussard ◽  
Pierre-Jean Saulnier ◽  
Louis Potier ◽  
Stéphanie Ragot ◽  
Fabrice Schneider ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Lower Extremity ◽  
Incidence Rate ◽  
Cox Regression ◽  
Arterial Disease ◽  
Lower Extremity Arterial Disease ◽  
C Statistic

<b>Objective. </b>We evaluated the association between diabetic retinopathy stages and lower-extremity arterial disease (LEAD), its prognostic value, and the influence of potential contributors in this relationship in a prospective cohort of patients with type 2 diabetes. <p><b>Research design and methods</b><b>. </b>Diabetic retinopathy was staged at baseline as absent, non-proliferative or proliferative. Cox regression model was fitted to compute HR (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. Retinopathy-LEAD association was assessed in subgroups by age, gender, diabetes duration, HbA1c, systolic blood pressure, diabetic kidney disease, smoking, and macrovascular disease at baseline. The performance of retinopathy to stratify LEAD risk was assessed using c-statistic, integrated discrimination improvement (IDI) and net reclassification improvement (NRI).<b></b></p> <p><b>Results. </b>Among 1320 participants without a baseline history of LEAD, 94 (7.1%) patients developed a major LEAD during a 7.1-year median follow-up (incidence rate 9.6, 95%CI [7.8–11.7] per 1000 person-years). The LEAD incidence rate increased by worsening retinopathy: absent 5.5 (3.9–7.8), non-proliferative 14.6 (11.1–19.3), proliferative 20.1 (11.1–36.3) per 1000 person-years. Compared with absent retinopathy, non-proliferative (multi-adjusted HR 2.31, 95%CI [1.43–3.81], p=0.0006) and proliferative retinopathy (3.14 [1.40–6.15], p=0.007) remained associated with major LEAD. No heterogeneity was observed across subgroups. Retinopathy enhanced c-statistic (+0.023 [0.003–0.044], p=0.02), IDI (0.209 [0.130 – 0.321], p<0.001) and NRI (0.562 [0.382– 0.799], p<0.001) for LEAD risk, beyond traditional risk factors.</p> <p><b>Conclusions. </b>An independent dose-response relationship was observed between diabetic retinopathy stages and major LEAD. Retinopathy yielded incremental prognostic information for LEAD risk stratification, suggesting its usefulness as LEAD predictor.<b></b></p>

scholarly journals Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study

2021 ◽  
Author(s):  
Maoxiang Zhao ◽  
Lulu Song ◽  
Lan Sun ◽  
Miao Wang ◽  
Chi Wang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cox Regression ◽  
Age Groups ◽  
Onset Age ◽  
Onset Type ◽  
Diabetes Onset ◽  
All Cause Mortality

<b>Objective</b><b></b> <p>We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in Chinese population.</p> <p><b>Research design and methods</b></p> <p>This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan study. All participants were followed biennially until December 31, 2017. A total of 11,384 participants were diagnosed as type 2 diabetes during follow-up. For each case, one control was randomly selected matched for age (±1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% confidence intervals (CIs) of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes <i>versus </i>controls across age groups.</p> <p><b>Results</b><b></b></p> <p>During a median follow-up of 5.57 years, 1794 incident events (907 CVD events, of which were 725 strokes, and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age < 45 years had the highest risks of CVD and all-cause mortality relative to the matched controls, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. </p> <p><b>Conclusions</b><b></b></p> <p>The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age groups, and the associations were more evident in younger-onset type 2 diabetes. </p>

Abstract P413: Chocolate Consumption is Associated with a Lower Risk of Heart Failure in Lean US Male Physicians

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Andrew B Petrone ◽  
J. Michael Gaziano ◽  
Luc Djousse
Keyword(s):  
Heart Failure ◽  
Lower Risk ◽  
Cox Regression ◽  
Secondary Analysis ◽  
Health Study ◽  
Adjusted Relative Risk ◽  
Hazard Ratios ◽  
Lower Blood ◽  
History Of

Background: Previous studies have suggested that dark chocolate consumption may lower blood pressure, a major risk factor for heart failure. However, limited and inconsistent data are available on the association of chocolate consumption with the incidence rate of heart failure. Objective: To test the hypothesis that chocolate consumption is associated with a lower risk of heart failure. Methods: We prospectively studied 20,278 men from the Physicians’ Health Study. Chocolate consumption was assessed between 1999 and 2002 via a food frequency questionnaire and heart failure was ascertained through annual follow-up questionnaires with validation in a subsample. We used Cox regression to estimate multivariable adjusted relative risk of heart failure. Results: During a median follow-up of 9.3 years, there were 876 new cases of heart failure. The mean age at baseline was 66.4 ± 9.2 years. Median chocolate consumption was 1-3 times per month. Hazard ratios (95% CI) for heart failure were 1.0 (ref), 0.87 (0.73-1.04), 0.80 (0.66-0.98), and 0.87 (0.72-1.04), for chocolate consumption of less than 1/month, 1-3/month, 1/week, and 2+/week, respectively, after adjusting for age, body mass index (BMI), smoking, alcohol intake, exercise, and history of atrial fibrillation. In a secondary analysis, chocolate consumption was inversely associated with risk of heart failure in men whose BMI was <25 kg/m 2 but not in those with BMI of 25+ kg/m 2 ( Figure 1 ), p for interaction=0.0895. Conclusions: Our data suggest that moderate consumption of chocolate might be associated with a lower risk of heart failure, especially in lean individuals.

scholarly journals Metformin reduces risk of benign nodular goiter in patients with type 2 diabetes mellitus

2019 ◽  
Vol 180 (6) ◽  
pp. 365-372 ◽  
Author(s):  
Chin-Hsiao Tseng
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Propensity Score ◽  
Lower Risk ◽  
Cox Regression ◽  
Nodular Goiter ◽  
Sensitivity Analyses ◽  
Hazard Ratios

BackgroundWhether metformin might affect the risk of benign nodular goiter in patients with type 2 diabetes mellitus has not been investigated.MethodsPatients with new-onset type 2 diabetes mellitus during 1999–2005 were enrolled from Taiwan’s National Health Insurance database. Analyses were conducted in a propensity score matched-pairs of 20,048 ever users and 20,048 never users of metformin. The patients were followed until December 31, 2011, for the incidence of benign nodular goiter. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using the propensity score.ResultsAmong the never users and ever users of metformin, 392 and 221 cases were diagnosed of benign nodular goiter during follow-up, with incidence of 457.88 and 242.45 per 100,000 person-years, respectively. The overall hazard ratio for ever versus never users was 0.527 (95% confidence interval: 0.447–0.621). When cumulative duration of metformin therapy was divided into tertiles, the hazard ratios for the first (<25.3 months), second (25.3–57.3 months) and third (>57.3 months) tertiles were 0.815 (0.643–1.034), 0.648 (0.517–0.812) and 0.255 (0.187–0.348), respectively. Sensitivity analyses estimating the overall hazard ratios for patients enrolled in each specific year from 1999 to 2005 consistently showed a lower risk of benign nodular goiter among users of metformin.ConclusionMetformin use is associated with a lower risk of benign nodular goiter in patients with type 2 diabetes mellitus.

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