Disclosures: Kathryn A Martin, MD Nothing to disclose. Jean E Mulder, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Effect of finerenone in diabetic nephropathy (October 2015)
Mineralocorticoid receptor antagonists (MRAs) reduce proteinuria in patients with diabetic nephropathy, whether used alone or in combination with an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Finerenone, an investigational nonsteroidal MRA that may be associated with less hyperkalemia than other MRAs, was evaluated in a phase 2 dose-finding trial of 823 patients with type 2 diabetes treated with an ACE inhibitor or ARB . A dose-dependent effect was observed at 90 days, with albuminuria reductions ranging from 21 to 38 percent at doses ranging from 7.5 mg/day to 20 mg/day. The incidence of hyperkalemia with finerenone treatment was low (1.5 percent); acute reductions in glomerular filtration rate were mild and were reversible after cessation of the study drug. The long-term effects of MRAs, including finerenone, in patients with diabetic nephropathy is unknown, and they should not be routinely used in these patients until such data are available. (See "Treatment of diabetic nephropathy", section on 'Mineralocorticoid receptor antagonism'.)
Empagliflozin in diabetic individuals with overt cardiovascular disease (September 2015)
The cardiovascular effects of diabetes drugs have been evaluated in a growing number of trials. In a trial designed to evaluate the sodium-glucose co-transporter 2 (SGLT-2) inhibitor empagliflozin and cardiovascular outcomes in patients with type 2 diabetes and established cardiovascular disease (CVD), 7028 patients were randomly assigned to empagliflozin or placebo once daily . The majority of patients were taking metformin, antihypertensives, and lipid-lowering agents, and approximately half in each group were taking insulin.
After three years, the primary outcome (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) occurred in fewer patients assigned to empagliflozin than to placebo (10.5 versus 12.1 percent), driven by a significant reduction in risk of death from cardiovascular causes (3.7 versus 5.9 percent). The difference in glycemia between the groups was minimal (glycated hemoglobin [A1C] 7.8 versus 8.2 percent), suggesting that extra-glycemic effects of the drug were responsible for the CVD outcome. Whether empagliflozin or other SGLT-2 inhibitors will have similar CVD effects in individuals with type 2 diabetes who do not have overt CVD is unknown. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'SGLT2 inhibitors'.)
Bariatric surgery for diabetic patients and glycemic control (September 2015)
Bariatric surgical treatment of obese patients with diabetes results in significant sustained weight loss (20 to 30 percent after one to two years) and, in parallel, large improvements in blood glucose control. However, there are few data on long-term success rates in maintaining weight loss and glucose control. In a report of five-year outcomes (53 patients) from a randomized trial evaluating gastric bypass, biliopancreatic diversion, or medical therapy (pharmacologic therapy, education, lifestyle modification) in 60 patients with obesity and type 2 diabetes, diabetes remission (A1C <6.5 percent without diabetes medication) was maintained in only 56 percent of patients in the surgical groups who had experienced remission at two years . Compared with the medical group, patients treated surgically had significantly lower diabetes and cardiovascular medication use, serum total and LDL cholesterol, and weight, although weight regain occurred in both surgical groups (+6.09 and +4.56 kg, respectively). The study was not powered to assess long-term diabetes complications. Longer-term follow-up of microvascular and macrovascular complications and mortality are required before laparoscopic banding or other bariatric surgery procedures can be routinely recommended for the treatment of persistent hyperglycemia in obesity-related type 2 diabetes. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'Surgical treatment of obesity'.)
SGLT2 inhibitors may predispose to DKA (July 2015)
Sodium-glucose co-transporter 2 (SGLT2) inhibitors promote the renal excretion of glucose and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes. “Euglycemic” (usually meaning plasma glucose <250 mg/dL) diabetic ketoacidosis (DKA) has been reported in patients with type 2 diabetes taking SGLT2 inhibitors [4,5]. The absence of substantial hyperglycemia delayed recognition of DKA by both the patients and the clinicians. Thus, serum ketones should be obtained in any patient with nausea, vomiting, or malaise while taking SGLT2 inhibitors, and SGLT2 inhibitors should be discontinued if acidosis is confirmed. A warning about SGLT2 inhibitors and ketoacidosis was issued by the US Food and Drug Administration in May 2015. Given the absence of long-term efficacy and safety data, we do not recommend SGLT2 inhibitors for routine use in patients with type 2 diabetes. In addition, off-label use in type 1 diabetes is discouraged in the absence of sufficient safety data. (See "Management of persistent hyperglycemia in type 2 diabetes mellitus", section on 'SGLT2 inhibitors'.)
DPP-4 inhibitors for diabetes and cardiovascular safety (June 2015)
A number of trials have evaluated the cardiovascular effects of DPP-4 inhibitors. In a recent large trial, 14,735 patients with type 2 diabetes and established cardiovascular disease were randomly assigned to sitagliptin or placebo, in addition to other diabetes medications (predominantly metformin, sulfonylurea, insulin) . After a median follow-up of three years, there was no difference in the primary composite cardiovascular outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina), individual components of the composite, or hospitalization rate for heart failure (3.1 percent in each group). Although these data are reassuring, longer-term clinical trials are needed to definitively assess the cardiovascular safety of DPP-4 inhibitors in patients with heart disease. In addition, there are no data on cardiovascular safety in lower-risk patients. With only modest glucose-lowering effectiveness and relative expense, we do not consider DPP-4 inhibitors as options for initial therapy in the majority of patients with type 2 diabetes. (See "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.)
Combination renin-angiotensin system inhibition in diabetic patients (June 2015)
Several randomized trials that directly compared dual versus single renin-angiotensin system inhibition in diabetic patients found that dual therapy produced no benefit and an increase in adverse effects. Findings are similar in a subsequent network meta-analysis . In this analysis in patients with diabetes and hypertension, dual therapy with an angiotensin-converting enzyme (ACE) inhibitor plus an angiotensin II receptor blocker (ARB) was superior to placebo in preventing end-stage renal disease, but monotherapy with either an ACE inhibitor or an ARB, also compared with placebo, produced similar benefits while dual therapy produced more adverse effects. Combination renin-angiotensin system inhibition with an ACE inhibitor and ARB or direct renin inhibitor is not recommended in diabetic patients. (See "Treatment of hypertension in patients with diabetes mellitus", section on 'Avoid combination renin-angiotensin system inhibition'.)
Frozen donor oocyte use impacts live birth rate (August 2015)
Use of donor oocytes (eggs) in assisted reproductive technology has allowed women unable to conceive with their own eggs the opportunity to achieve pregnancy. The use of frozen oocytes is more convenient and less costly compared with fresh oocytes because the donor and recipient don't have to be hormonally synchronized and frozen eggs can be shipped anywhere. Although initial studies reported equivalent pregnancy and live birth rates for donor egg transfers, a study of over 11,000 oocyte donation cycles, including 20 percent using frozen eggs, reported the live birth rate per transfer for frozen donor oocytes was lower than the live birth rate for fresh donor oocytes (47 versus 56 percent) . Despite the possible discrepancy in live birth rate, the improved efficiency and lower cost of cryopreserved donor oocytes makes their use a reasonable and attractive option. (See "Management of infertility and pregnancy in women of advanced age", section on 'Oocyte or embryo donation'.)
Medication approved for low sexual desire in women (August 2015)
Flibanserin is the first and currently only drug approved by the US Food and Drug Administration (FDA) for female sexual dysfunction . Daily use results in modest increases in the frequency of sexually satisfying events and sexual desire. The clinical role of flibanserin may be limited by the need for daily dosing, common adverse effects (eg, somnolence, dizziness), and by safety concerns or lack of safety data regarding combining flibanserin with alcohol or certain medications (eg, fluconazole, CYP3A4 inhibitors, antidepressants). (See "Sexual dysfunction in women: Management", section on 'Flibanserin'.)
Fertility among survivors of childhood Hodgkin lymphoma (June 2015)
Counseling regarding infertility risks associated with Hodgkin lymphoma (HL) therapy is important for HL survivors of childbearing age. The impact of regimens used for childhood HL on long-term fertility was evaluated in a prospective study of over 450 female survivors of childhood HL in continuous remission with a median follow-up of 20 years . For those younger than age 40, the likelihood of parenthood was similar to an age-matched German population. Factors associated with a decreased likelihood of successful pregnancy included age over 40 years and receipt of pelvic radiation. These results should be reassuring to HL survivors. (See "Overview of the approach to the adult survivor of classical Hodgkin lymphoma", section on 'Gonadal dysfunction'.)
Testosterone injectables versus gels and cardiovascular risk (June 2015)
Concerns have been raised that testosterone therapy in men may be associated with an increase in cardiovascular risk. Available data now suggest that the route of testosterone administration may be associated with the excess risk. In a retrospective analysis of three databases of over 544,000 men receiving newly prescribed testosterone therapy, use of injectable testosterone preparations (which result in intermittent supraphysiologic serum testosterone concentrations) was associated with a greater risk of myocardial infarction (MI) and stroke, but not venous thromboembolism, when compared with testosterone gel use . Of note, the absolute risks associated with testosterone injectables were low, and the study did not compare the rate of cardiovascular events in testosterone users versus nonusers. These data do not change our management approach. We typically suggest testosterone gels, but some men prefer injectables because of their lower cost and convenience. (See "Testosterone treatment of male hypogonadism", section on 'Cardiovascular risks'.)
X-linked TEX11 mutations and azoospermia (May 2015)
Y-chromosome defects and a number of autosomal and X-linked gene mutations are increasingly recognized as genetic causes of azoospermia and severe oligospermia. X-linked TEX11 mutations have now been identified as an important cause of meiotic arrest and azoospermia in infertile men . In a report, hemizygous TEX11 mutations on chromosome Xq13.2 were identified in 7 of 289 men with azoospermia (2.4 percent). In testes from normal men, immunohistochemical analysis showed TEX11 expression in late spermatocytes, and in round and elongated spermatids. Testes from patients with azoospermia and TEX11 mutations had meiotic arrest and no TEX11 expression. (See "Causes of male infertility", section on 'Autosomal and X chromosome defects'.)
Menopausal hormone therapy: Endocrine Society clinical practice guideline (October 2015)
Menopausal hormone therapy (MHT) continues to play an important role in the management of hot flashes. A new clinical practice guideline, published by the Endocrine Society, presents an individualized approach to the management of menopausal symptoms based upon calculating a woman’s baseline cardiovascular and breast cancer risks prior to initiating therapy . Similar to many other guidelines, the Endocrine Society suggests that MHT is indicated for the management of menopausal symptoms, but not for the prevention of cardiovascular disease, osteoporosis, or dementia. (See "Menopausal hormone therapy: Benefits and risks", section on 'Guidelines'.)
Menopausal hormone therapy and cardiovascular risk: Timing of exposure (June 2015)
Current evidence suggests that the use of menopausal hormone therapy (MHT) in the early menopausal years (<10 years from menopause) may not be associated with excess cardiovascular risk when compared with use in the later menopausal years. This has been referred to as the "timing hypothesis." Additional support for this hypothesis comes from a 2015 meta-analysis of 19 trials of oral (including the Womens Health Initiative), but not transdermal, MHT in over 40,000 postmenopausal women . A subgroup analysis in women who started MHT less than 10 years after menopause showed a lower risk of coronary heart disease (CHD) compared with placebo (RR 0.52; 8 fewer cases of heart disease per 1000 women treated/year) and a lower mortality rate (RR 0.70; 6 fewer deaths per 1000 women treated/year). However, there were important limitations in this analysis; when one methodologically flawed trial was removed, the beneficial effects on CHD and mortality were no longer significant (but no adverse effects were seen). These data provide additional evidence that oral MHT use in younger postmenopausal women is not associated with excess CHD risk. (See "Menopausal hormone therapy: Benefits and risks", section on 'Younger postmenopausal women'.)
Menopausal hormone therapy effect on cognition and mood in younger menopausal women (June 2015)
Menopausal hormone therapy (MHT) in older menopausal women (>65 years) has an adverse effect on cognitive function and an inconsistent effect on mood. The KEEPS study (Kronos Early Estrogen Prevention Study), a trial of menopausal hormone therapy (MHT) in younger menopausal women ages 45 to 54 years who underwent extensive cognitive and mood testing, reported that four years of MHT had no overall effect on cognition when compared with placebo . However, oral estrogen appeared to improve mood, as women receiving oral conjugated estrogen combined with micronized progesterone had lower depression and anxiety scores than those receiving either transdermal estradiol (with micronized progesterone) or placebo. (See "Menopausal hormone therapy: Benefits and risks", section on 'Cognitive function and dementia'.)
Intragastric balloon device for weight loss (October 2015)
Intragastric balloon devices, which are placed endoscopically and promote a feeling of satiety and food restriction, can result in modest weight loss and have been available outside of the United States. One such device, the ReShape Integrated Dual Balloon System, was recently approved by the US Food and Drug Administration to treat obesity in adults with a body mass index (BMI) of 30 to 40 kg/m2 and one or more comorbid conditions such as diabetes, hypertension, or hypercholesterolemia. It is intended for patients who have failed previous attempts at weight loss through diet and exercise alone and is generally left in place for a maximum of six months. In a trial of 326 patients with BMI 30 to 40 kg/m2, those who were randomly assigned to ReShape balloon placement lost more weight than the control group, who received endoscopy without balloon insertion (6.8 versus 3.3 percent of total body weight) . Six months after removal of the device, patients maintained 70 percent of their initial weight loss. (See "Bariatric procedures for the management of severe obesity: Descriptions", section on 'Expected weight loss IGB'.)
FTO variant and obesity (September 2015)
Large genome wide association studies have demonstrated that variants in the FTO gene have the strongest association with obesity risk in the general population, but the mechanism of the association has been unclear. However, a nonocoding causal variant in FTO has now been identified that changes the function of adipocytes from energy utilization (beige fat) to energy storage (white fat) with a fivefold decrease in mitochondrial thermogenesis . When the effect of the variant was blocked in genetically engineered mice, thermogenesis increased and weight gain did not occur, despite eating a high-fat diet. Blocking the gene's effect in human adipocytes also increased energy utilization. This observation has important implications for potential new anti-obesity drugs. (See "Pathogenesis of obesity", section on 'FTO variants'.)
Liraglutide for the treatment of obesity (July 2015)
Along with diet, exercise, and behavior modification, drug therapy may be a helpful component of treatment for select patients who are overweight or obese. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, used for the treatment of type 2 diabetes, and can promote weight loss in patients with diabetes, as well as those without diabetes.
●In a randomized trial in nondiabetic patients who had a body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 with dyslipidemia and/or hypertension, liraglutide 3 mg once daily, compared with placebo, resulted in greater mean weight loss (-8.0 versus -2.6 kg with placebo) . In addition, cardiometabolic risk factors, glycated hemoglobin (A1C), and quality of life improved modestly. Gastrointestinal side effects transiently affected at least 40 percent of the liraglutide group and were the most common reason for withdrawal (6.4 percent). Liraglutide is an option for select overweight or obese patients, although gastrointestinal side effects (nausea, vomiting) and the need for a daily injection may limit the use of this drug. (See "Obesity in adults: Drug therapy", section on 'Liraglutide'.)
●In a trial designed specifically to evaluate the effect of liraglutide on weight loss in overweight or obese patients with type 2 diabetes (mean weight 106 kg), liraglutide, compared with placebo, resulted in greater mean weight loss (-6.4 kg and -5.0 kg for liraglutide 3 mg and 1.8 mg, respectively, versus -2.2 kg for placebo) . Treatment with liraglutide was associated with better glycemic control, a reduction in the use of oral hypoglycemic agents, and a reduction in systolic blood pressure. Although liraglutide is not considered as initial therapy for the majority of patients with type 2 diabetes, it is an option for select overweight or obese patients with type 2 diabetes who fail initial therapy with lifestyle intervention and metformin. (See "Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus", section on 'Weight loss'.)
Subclinical hyperthyroidism and fracture risk (July 2015)
Patients with subclinical hyperthyroidism have normal serum concentrations of free thyroxine (T4) and triiodothyronine (T3), but subnormal concentrations of thyroid-stimulating hormone (TSH). Common causes of subclinical hyperthyroidism include autonomously functioning thyroid adenomas and multinodular goiters, Graves’ disease, or excessive thyroid hormone therapy. Subclinical hyperthyroidism is associated with reduced bone density, particularly in cortical-rich bone in postmenopausal women. The risk of fracture has been less certain. A meta-analysis of 13 prospective cohort studies showed that compared with euthyroidism, endogenous subclinical hyperthyroidism (autonomy or Graves' disease) was associated with an increased risk of hip fracture (6.1 versus 4.4 percent) . In this analysis, lower TSH levels (<0.10 mU/L) were associated with higher fracture rates. (See "Bone disease with hyperthyroidism and thyroid hormone therapy", section on 'Fracture risk'.)
Vitamin D supplementation during pregnancy (May 2015)
Several observational studies suggest an association between poor maternal vitamin D status and adverse pregnancy outcomes. A meta-analysis of 13 trials showed that, compared with a control group, vitamin D administration (in varied dosing, types, and schedules) resulted in higher serum 25(OH)D levels at delivery but no difference in the incidence rates of preeclampsia or gestational diabetes . There was also no difference in the incidence rates of small for gestational age, low birth weight, and preterm birth in the neonates. Although routine prenatal vitamin D supplementation does not appear to prevent low birthweight, preterm birth, or preeclampsia, the earliest interventions in the published trials were made in the late first trimester. Initiation of therapy with vitamin D prior to conception has not been evaluated. (See "Vitamin D and extraskeletal health", section on 'Pregnancy outcomes'.)
Enzyme replacement therapy for hypophosphatasia (November 2015)
Hypophosphatasia is a rare, autosomal disease that is associated with low levels of alkaline phosphatase in serum and bone and the development of osteomalacia and severe periodontal disease. It may present in the perinatal period, when it is lethal; in infancy, where rachitic deformities develop by age six months; in childhood, with premature loss of deciduous teeth, delayed walking, and waddling gait; or in adulthood, where it is characterized by the presence of recurrent metatarsal stress fractures and bone pain, and an increased incidence of chondrocalcinosis. Historically, there have been few treatment options. However, enzyme replacement therapy (asfotase alfa) for perinatal, infantile, and juvenile-onset hypophosphatasia became available in October 2015, based upon the results of open-label prospective studies in 99 patients with perinatal, infantile, or juvenile-onset hypophosphatasia, in whom enzyme replacement therapy was associated with improved overall survival, ventilator-free survival, growth, and bone mineralization compared with a historic cohort . (See "Clinical manifestations, diagnosis, and treatment of osteomalacia", section on 'Other causes'.)
PCSK9 antibodies for cardiovascular risk reduction (September 2015)
Monoclonal antibodies that inhibit proprotein convertase subtilisin kexin 9 (PCSK9-abs) reduce LDL-cholesterol levels by as much as 70 percent. Randomized trials with small numbers of events and limited follow-up suggest that at least two of these agents, alirocumab and evolocumab, substantially reduce cardiovascular events and mortality when used for secondary prevention, both as monotherapy and in combination with statin therapy [23,24]. (See "Lipid lowering with drugs other than statins and fibrates", section on 'PCSK9 inhibitors'.)
PCSK9-abs are becoming available for clinical use. The agents require subcutaneous injection every two to four weeks and are very expensive. While awaiting greater experience with these agents, we would use them in situations where the expected reductions in cardiovascular events are likely to outweigh any as yet unknown adverse events from a new therapy. These include using them in combination with statin therapy in very high-risk patients with stable cardiovascular disease, such as those in the proposed NCEP guidelines (table 1), and as monotherapy in very high-risk and higher-risk patients who are intolerant of statin therapy. Other experts, including other authors for UpToDate, would make decisions about adding medications to statin therapy based on goal LDL-cholesterol. (See "Intensity of lipid lowering therapy in secondary prevention of cardiovascular disease", section on 'Stable CVD' and "Treatment of lipids (including hypercholesterolemia) in secondary prevention", section on 'Summary and recommendations'.)
- Bakris GL, Agarwal R, Chan JC, et al. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial. JAMA 2015; 314:884.
- Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015.
- Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric-metabolic surgery versus conventional medical treatment in obese patients with type 2 diabetes: 5 year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2015; 386:964.
- Peters AL, Buschur EO, Buse JB, et al. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care 2015; 38:1687.
- Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab 2015; 100:2849.
- Green JB, Bethel MA, Armstrong PW, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2015; 373:232.
- Palmer SC, Mavridis D, Navarese E, et al. Comparative efficacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis. Lancet 2015; 385:2047.
- Kushnir VA, Barad DH, Albertini DF, et al. Outcomes of Fresh and Cryopreserved Oocyte Donation. JAMA 2015; 314:623.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm458734.htm (Accessed on August 24, 2015).
- Brämswig JH, Riepenhausen M, Schellong G. Parenthood in adult female survivors treated for Hodgkin's lymphoma during childhood and adolescence: a prospective, longitudinal study. Lancet Oncol 2015; 16:667.
- Layton JB, Meier CR, Sharpless JL, et al. Comparative Safety of Testosterone Dosage Forms. JAMA Intern Med 2015; 175:1187.
- Yatsenko AN, Georgiadis AP, Röpke A, et al. X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med 2015; 372:2097.
- Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100:3975.
- Boardman HM, Hartley L, Eisinga A, et al. Hormone therapy for preventing cardiovascular disease in post-menopausal women. Cochrane Database Syst Rev 2015; 3:CD002229.
- Gleason CE, Dowling NM, Wharton W, et al. Effects of Hormone Therapy on Cognition and Mood in Recently Postmenopausal Women: Findings from the Randomized, Controlled KEEPS-Cognitive and Affective Study. PLoS Med 2015; 12:e1001833; discussion e1001833.
- Ponce J, Woodman G, Swain J, et al. The REDUCE pivotal trial: a prospective, randomized controlled pivotal trial of a dual intragastric balloon for the treatment of obesity. Surg Obes Relat Dis 2015; 11:874.
- Claussnitzer M, Dankel SN, Kim KH, et al. FTO Obesity Variant Circuitry and Adipocyte Browning in Humans. N Engl J Med 2015; 373:895.
- Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med 2015; 373:11.
- Davies MJ, Bergenstal R, Bode B, et al. Efficacy of Liraglutide for Weight Loss Among Patients With Type 2 Diabetes: The SCALE Diabetes Randomized Clinical Trial. JAMA 2015; 314:687.
- Blum MR, Bauer DC, Collet TH, et al. Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA 2015; 313:2055.
- Pérez-López FR, Pasupuleti V, Mezones-Holguin E, et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2015; 103:1278.
- http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468836.htm (Accessed on October 29, 2015).
- Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med 2015; 163:40.
- Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372:1500.