Search

Purpose: To systematically review the evidence on benefits and harms of (1) screening for abnormal blood glucose and type 2 diabetes and (2) interventions for prediabetes or type 2 diabetes that was screen detected or recently diagnosed for populations and settings relevant to primary care in the United States., Data Sources: PubMed/MEDLINE, the Cochrane Library, and trial registries through September 10, 2019; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through May 21, 2021., Study Selection: English-language controlled studies evaluating screening for abnormal blood glucose or evaluating interventions for prediabetes or type 2 diabetes that was screen detected or recently diagnosed., Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for all included studies using predefined criteria., Data Synthesis: This review included 89 publications. Two randomized, controlled trials (RCTs) (ADDITION-Cambridge and Ely; described in 5 articles; 25,120 participants) evaluated invitations to screening for diabetes with (1) a stepwise approach (starting with random glucose) or (2) oral glucose tolerance test every 5 years. The trials found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years or self-reported cardiovascular disease (CVD) events or quality of life at 7 through 13 years, but the trials were missing data from most participants for outcomes other than mortality. For harms, the trials reported no significant differences between screening and control groups for anxiety, depression, worry, or self-reported health, but one reported a short-term increase in anxiety (at 6 weeks) among persons screened and diagnosed with diabetes mellitus (DM) versus those not diagnosed with DM (State-Trait Anxiety Inventory scores: 46.7 vs. 37.0; p=0.031). For screen-detected diabetes, one trial (ADDITION-Europe, described in 8 articles, 3,057 participants) evaluated a multifactorial intervention aimed at controlling glucose, blood pressure, and cholesterol and found no difference over 5 years in the risk of all-cause mortality, cardiovascular-related mortality, cardiovascular events, or other health outcomes between intervention and routine care groups. A post hoc analysis at about 10-years followup similarly found that differences remained nonsignificant for the primary composite outcome and for all-cause mortality. For recently diagnosed (not screen-detected) diabetes, five RCTs (8 publications, 5,138 participants) were included. In the United Kingdom Prospective Diabetes Study, long-term health outcomes were improved with intensive glucose control with sulfonylureas or insulin: decreased risk for all-cause mortality (relative risk [RR], 0.87 [95% confidence interval {CI}, 0.79 to 0.96]), diabetes-related mortality (RR, 0.83 [95% CI, 0.73 to 0.96]), and myocardial infarction (RR, 0.85 [95% CI, 0.74 to 0.97]) over 20 years (10-year post-trial assessment) but not at shorter followups. For overweight people, intensive glucose control with metformin decreased the risk for all-cause mortality (RR, 0.64 [95% CI, 0.45 to 0.91]), diabetes-related mortality [RR, 0.58 [95% CI, 0.37 to 0.91]), and myocardial infarction (RR, 0.61 [95% CI, 0.41 to 0.89]) at the 10-year followup, and benefits were maintained longer term. For prediabetes interventions, most trials reporting on health outcomes had insufficient duration of followup for long-term health outcomes, reported few events, and found no difference between groups. One trial of a 6-year lifestyle intervention conducted in China (Da Qing, n=576) reported lower all-cause mortality (28.1% vs. 38.4% [hazard ratio {HR}, 0.71 {95% CI, 0.51 to 0.99}]) and CVD-related mortality (11.9% vs. 19.6% [HR, 0.59 {95% CI, 0.36 to 0.96}]) for intervention groups than for controls at 23 years but not at earlier followups; 30-year followup also reported lower all-cause mortality (HR, 0.74 [95% CI, 0.61 to 0.89]) and CVD-related mortality (HR, 0.67 [95% CI, 0.48 to 0.94]) for intervention groups than for controls. Lifestyle interventions (most involving >360 minutes contact) for obese or overweight people with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs, pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with reduced systolic blood pressure and diastolic blood pressure (pooled weighted mean difference [WMD] −1.7 mm hg [95% CI, −2.6 to −0.8] and −1.2 mm hg [95% CI, −2.0 to −0.4], respectively), weight (pooled WMD, −1.2 kg [95% CI, −1.6 to −0.74]), and body mass index (BMI) (pooled WMD, −0.54 kg/m 2 [95% CI, −0.76 to −0.33]). For medications, metformin, thiazolidinediones (TZDs), and alpha glucosidase inhibitors (AGIs) were associated with a reduction in diabetes incidence (pooled RRs, 0.73 [0.64, 0.83], 0.50 [0.28, 0.92], and 0.64 [0.43, 0.96], respectively), but evidence for TZDs and AGIs was limited by imprecision, inconsistency, and risk of bias. Most trials of medications found no statistically significant association between hypoglycemic agents and changes in blood pressure or lipids, but they did find a reduction in weight and BMI for metformin, acarbose, or liraglutide, but TZDs were associated with weight gain (pooled WMD, 1.9 kg [95% CI, 0.8 to 3.1])., Limitations: No trials assessed initial screening with A1c or fasting glucose and none assessed screening for prediabetes. For outcomes other than mortality, screening trials were missing data from most participants. Duration of followup was too short to assess health outcomes in most studies. A single trial evaluated interventions for screen-detected diabetes. The Da Qing trial conducted in China (n=576 participants enrolled in 1986) has not been replicated and was limited by at least medium risk of bias because of unclear randomization and allocation concealment methods and baseline differences likely to bias results in favor of the intervention. Harms were rarely assessed; none of the trials reported on labeling, harms from false-positive results, burden, inconvenience, or unnecessary testing and treatment., Conclusions: Trials of screening for diabetes found no mortality benefit at 10 years but had insufficient data to assess other health outcomes. Evidence on harms of screening was scant. For people with screen-detected diabetes, one trial found no improvement in health outcomes over 5 to 10 years. For people with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes over 10 to 20 years. For obese or overweight people with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes, and limited evidence suggests that very high contact lifestyle interventions improve health outcomes after more than 20 years.

Background: Untreated maternal mental health disorders can have devastating sequelae for the mother and child. For women who are currently or planning to become pregnant or are breastfeeding, a critical question is whether the benefits of treating psychiatric illness with pharmacologic interventions outweigh the harms for mother and child., Methods: We conducted a systematic review to assess the benefits and harms of pharmacologic interventions compared with placebo, no treatment, or other pharmacologic interventions for pregnant and postpartum women with mental health disorders. We searched four databases and other sources for evidence available from inception through June 5, 2020 and surveilled the literature through March 2, 2021; dually screened the results; and analyzed eligible studies. We included studies of pregnant, postpartum, or reproductive-age women with a new or preexisting diagnosis of a mental health disorder treated with pharmacotherapy; we excluded psychotherapy. Eligible comparators included women with the disorder but no pharmacotherapy or women who discontinued the pharmacotherapy before pregnancy., Results: A total of 164 studies (168 articles) met eligibility criteria. Brexanolone for depression onset in the third trimester or in the postpartum period probably improves depressive symptoms at 30 days (least square mean difference in the Hamilton Rating Scale for Depression, −2.6; p=0.02; N=209) when compared with placebo. Sertraline for postpartum depression may improve response (calculated relative risk [RR], 2.24; 95% confidence interval [CI], 0.95 to 5.24; N=36), remission (calculated RR, 2.51; 95% CI, 0.94 to 6.70; N=36), and depressive symptoms (p-values ranging from 0.01 to 0.05) when compared with placebo. Discontinuing use of mood stabilizers during pregnancy may increase recurrence (adjusted hazard ratio [AHR], 2.2; 95% CI, 1.2 to 4.2; N=89) and reduce time to recurrence of mood disorders (2 vs. 28 weeks, AHR, 12.1; 95% CI, 1.6 to 91; N=26) for bipolar disorder when compared with continued use. Brexanolone for depression onset in the third trimester or in the postpartum period may increase the risk of sedation or somnolence, leading to dose interruption or reduction when compared with placebo (5% vs. 0%). More than 95 percent of studies reporting on harms were observational in design and unable to fully account for confounding. These studies suggested some associations between benzodiazepine exposure before conception and ectopic pregnancy; between specific antidepressants during pregnancy and adverse maternal outcomes such as postpartum hemorrhage, preeclampsia, and spontaneous abortion, and child outcomes such as respiratory issues, low Apgar scores, persistent pulmonary hypertension of the newborn, depression in children, and autism spectrum disorder; between quetiapine or olanzapine and gestational diabetes; and between benzodiazepine and neonatal intensive care admissions. Causality cannot be inferred from these studies. We found insufficient evidence on benefits and harms from comparative effectiveness studies, with one exception: one study suggested a higher risk of overall congenital anomalies (adjusted RR [ARR], 1.85; 95% CI, 1.23 to 2.78; N=2,608) and cardiac anomalies (ARR, 2.25; 95% CI, 1.17 to 4.34; N=2,608) for lithium compared with lamotrigine during first-trimester exposure., Conclusions: Few studies have been conducted in pregnant and postpartum women on the benefits of pharmacotherapy; many studies report on harms but are of low quality. The limited evidence available is consistent with some benefit, and some studies suggested increased adverse events. However, because these studies could not rule out underlying disease severity as the cause of the association, the causal link between the exposure and adverse events is unclear. Patients and clinicians need to make an informed, collaborative decision on treatment choices.