BackgroundMedications that impact insulin sensitivity or cause weight gain may increase heart failure risk. Our aim was to compare heart failure and cardiovascular death outcomes among patients initiating sulfonylureas for diabetes mellitus treatment versus metformin.Methods and ResultsNational Veterans Health Administration databases were linked to Medicare, Medicaid, and National Death Index data. Veterans aged ≥18 years who initiated metformin or sulfonylureas between 2001 and 2011 and whose creatinine was <1.4 (females) or 1.5 mg/dL (males) were included. Each metformin patient was propensity score‐matched to a sulfonylurea initiator. The outcome was hospitalization for acute decompensated heart failure as the primary reason for admission or a cardiovascular death. There were 126 867 and 79 192 new users of metformin and sulfonylurea, respectively. Propensity score matching yielded 65 986 per group. Median age was 66 years, and 97% of patients were male; hemoglobin A1c 6.9% (6.3, 7.7); body mass index 30.7 kg/m2 (27.4, 34.6); and 6% had heart failure history. There were 1236 events (1184 heart failure hospitalizations and 52 cardiovascular deaths) among sulfonylurea initiators and 1078 events (1043 heart failure hospitalizations and 35 cardiovascular deaths) among metformin initiators. There were 12.4 versus 8.9 events per 1000 person‐years of use (adjusted hazard ratio 1.32, 95%CI 1.21, 1.43). The rate difference was 4 heart failure hospitalizations or cardiovascular deaths per 1000 users of sulfonylureas versus metformin annually.ConclusionsPredominantly male patients initiating treatment for diabetes mellitus with sulfonylurea had a higher risk of heart failure and cardiovascular death compared to similar patients initiating metformin.

IMPORTANCE Before 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown. OBJECTIVE To compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174 882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m 2 or creatinine Ն1.4 mg/dL for women or Ն1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016). EXPOSURES New users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function. MAIN OUTCOMES AND MEASURES MACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death. RESULTS There were 67 749 metformin and 28 976 sulfonylurea persistent monotherapy users; the weighted cohort included 24 679 metformin and 24 799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48 497 men [98%]; and 40 476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m 2 [IQR, 51.6-58.2] and hemoglobin A 1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use. CONCLUSIONS AND RELEVANCE Among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.

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Purpose of review-Over-prescribing opioids contributes to the epidemic of drug overdoses and deaths in the United States. Opioids are commonly prescribed after childbirth especially after cesarean, the most common major surgery. This review summarizes recent literature on patterns of opioid over-prescribing and consumption after childbirth, the relationship between opioid prescribing and chronic opioid use, and interventions that can help reduce over-prescribing. Recent findings-It is estimated that more than 80% of women fill opioid prescriptions after cesarean birth and about 54% of women after vaginal birth, although these figures vary greatly by geographical location and setting. After opioid prescriptions are filled, the median number of tablets used after cesarean is roughly 10 tablets and the majority of opioids dispensed (median 30 tablets) go unused. The quantity of opioid prescribed influences the quantity of opioid used. The risk of chronic opioid use related to opioid prescribing after birth may seem not high (annual risk: 0.12-0.65%) but the absolute number of women who are exposed to opioids after childbirth and become chronic opioid users every year is very large. Tobacco use, public insurance, and depression are associated with chronic opioid use after childbirth. The risk of chronic opioid use among women who underwent cesarean and received opioids after birth is not different from the risk of women who received opioids after vaginal delivery. Summary-Women are commonly exposed to opioids after birth. This exposure leads to an increased risk of chronic opioid use. Physician and providers should judiciously reduce the amount of opioids prescribed after childbirth, although more research is needed to identify the optimal method to reduce opioid exposure without adversely affecting pain management.

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ObjectivesWe aimed to validate an algorithm using both primary discharge diagnosis (International Classification of Diseases Ninth Revision (ICD-9)) and diagnosis-related group (DRG) codes to identify hospitalisations due to decompensated heart failure (HF) in a population of patients with diabetes within the Veterans Health Administration (VHA) system.DesignValidation study.SettingVeterans Health Administration—Tennessee Valley Healthcare SystemParticipantsWe identified and reviewed a stratified, random sample of hospitalisations between 2001 and 2012 within a single VHA healthcare system of adults who received regular VHA care and were initiated on an antidiabetic medication between 2001 and 2008. We sampled 500 hospitalisations; 400 hospitalisations that fulfilled algorithm criteria, 100 that did not. Of these, 497 had adequate information for inclusion. The mean patient age was 66.1 years (SD 11.4). Majority of patients were male (98.8%); 75% were white and 20% were black.Primary and secondary outcome measuresTo determine if a hospitalisation was due to HF, we performed chart abstraction using Framingham criteria as the referent standard. We calculated the positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for the overall algorithm and each component (primary diagnosis code (ICD-9), DRG code or both).ResultsThe algorithm had a PPV of 89.7% (95% CI 86.8 to 92.7), NPV of 93.9% (89.1 to 98.6), sensitivity of 45.1% (25.1 to 65.1) and specificity of 99.4% (99.2 to 99.6). The PPV was highest for hospitalisations that fulfilled both the ICD-9 and DRG algorithm criteria (92.1% (89.1 to 95.1)) and lowest for hospitalisations that fulfilled only DRG algorithm criteria (62.5% (28.4 to 96.6)).ConclusionsOur algorithm, which included primary discharge diagnosis and DRG codes, demonstrated excellent PPV for identification of hospitalisations due to decompensated HF among patients with diabetes in the VHA system.

Aim To evaluate whether recent low adherence to metformin monotherapy is associated with hypoglycaemia after addition of a sulfonylurea. Methods We assembled a retrospective cohort of veterans who filled a new prescription for metformin between 2001 and 2011 and intensified treatment with a sulfonylurea after ≥1 year of metformin use. We calculated metformin adherence from pharmacy data using the proportion of days covered in the 180‐day period before intensification. The primary outcome was hypoglycaemia, defined as a hospitalization or emergency department visit for hypoglycaemia or an outpatient blood glucose measurement <3.3 mmol/l in the year following intensification. Cox proportional hazards models were used to compare the risk of hypoglycaemia between participants with low (<80%) and high (≥80%) adherence. Adherence was also modelled as a continuous variable using restricted cubic splines. Results Of 187 267 participants who initiated metformin monotherapy, 49 424 added a sulfonylurea after ≥1 year. The median (interquartile range) rate of treatment adherence was 87 (50–100)% and 43% had adherence <80%. Hypoglycaemia rates per 1000 person‐years were 23.1 (95% CI 21.1–25.4) and 24.5 (95% CI 22.7–26.4) in participants with low and high adherence, respectively (adjusted hazard ratio 0.95, 95% CI 0.84–1.08). The risk of hypoglycaemia was similar across all levels of adherence when adherence was modelled as a continuous variable. Conclusions We found no evidence that past low adherence to metformin monotherapy was associated with hypoglycaemia after intensification with a sulfonylurea.

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