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The obesity and type 2 diabetes mellitus epidemics demonstrate that simply emphasizing a healthy lifestyle is insufficient. While weight loss medications have historically been considered “cosmetic”, glucagon-like peptide-1 receptor agonists (GLP1-RAs) also reduce cardiovascular risk in patients with type 2 diabetes. Therefore, we assessed whether GLP1-RAs warrant use in patients who are overweight (body mass index 27.0–29.9 kg/m2) without weight-related comorbidity. We reviewed trials of available GLP1-RAs with a natural GLP1 backbone given their trend toward cardiovascular benefit and excluded trials requiring concurrent antidiabetic agents associated with weight gain. We assessed 20 phase III trials of GLP1-RAs studied in cardiovascular outcome trials. The GLP1-RAs consistently produced weight loss. Hypoglycemia risk with GLP1-RAs was generally low without other precipitating factors, whereas gastrointestinal adverse effects were common. Dulaglutide 1.5 mg weekly did not produce sufficient weight loss to support its use specifically for weight loss, while data supporting dulaglutide 3.0 or 4.5 mg weekly were limited to a single trial. Weight loss was sufficient with liraglutide 1.8 mg daily in one trial and was consistently sufficient with liraglutide 3.0 mg daily. Oral and injectable semaglutide at both doses consistently produced weight loss, though demonstrated a potential increased risk for retinopathy. Overall, we suggest five GLP1-RAs can be used in the treatment of overweight (body mass index 27.0–29.9 kg/m2 without weight-related comorbidity) with shared decision making to address each medications’ key limitation: liraglutide 1.8 mg daily (less demonstrated weight loss), liraglutide 3.0 mg daily (no cardiovascular outcome trial at this dose), and oral and injectable semaglutide at both doses (uncertain retinopathy risk and pending cardiovascular outcome trial of high-dose semaglutide). Use should be limited to patients who fail, refuse, or cannot access lifestyle interventions for weight loss, and should be accompanied by standard restrictions on and monitoring of weight loss medications. We expect additional and earlier use of weight loss therapies to help clinicians curb the obesity and type 2 diabetes epidemics.

A growing number of antidiabetic agents have demonstrated cardiovascular and renal benefits in cardiovascular outcome trials (CVOTs), despite such trials being principally required to rule out excess cardiovascular risk.This article addresses the Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes (VERTIS-CV) trial, its background, design, results, and implications. In patients at least 40 years of age with atherosclerotic cardiovascular disease (ASCVD), the VERTIS-CV trial demonstrated ertugliflozin was non-inferior to placebo for major adverse cardiovascular events, though not superior. Ertugliflozin significantly reduced hospitalization for heart failure compared to placebo. The composite renal outcome was not significantly different between groups. Ertugliflozin was generally well tolerated with a safety profile commensurate with other sodium-glucose co-transporter-2 inhibitors (SGLT-2) inhibitors.In patients with type 2 diabetes and ASCVD, ertugliflozin appears safe with a noted non-significant trend toward improved renal outcomes. Approximately 23.7% of patients in the VERTIS-CV trial had heart failure, the highest among SGLT-2 inhibitor CVOTs. The VERTIS-CV trial reaffirms the reduction in heart failure hospitalizations as a likely class effect of SGLT-2 inhibitors. While the trial supports the use of ertugliflozin beyond glycemic control, agents with confirmed superiority for improved cardiovascular outcomes and mortality may be preferred.

Introduction: Eighty-four million patients in the United States have prediabetes yet evidence-based interventions to prevent diabetes are infrequently used. The concept of prediabetes is contentious, although preventive interventions are guideline supported. Team-based care models incorporating pharmacists for prediabetes have been proposed; however, pharmacist perception regarding prediabetes has not been assessed. This study's objective was to assess ambulatory care pharmacists’ perception of recommendations for prediabetes. Methods: An anonymous survey was electronically distributed through the American College of Clinical Pharmacy Ambulatory Care Practice and Research Network. The primary outcome was the proportion of respondents who reported supporting 3 main recommendations related to prediabetes (ie, screening, evidence-based lifestyle-intervention, metformin). The study was approved by the University of South Florida Institutional Review Board. Data collection and analysis occurred in 2017. Results: The survey was distributed to approximately 2209 potential participants. One hundred thirty-three surveys were completed. The American Diabetes Association guideline was the most common primarily supported guideline related to prediabetes (89%). Of the respondents, 87% supported all 3 main recommendations regarding prediabetes. Qualitative feedback demonstrated the full range of opinions; programs for prediabetes, limited intervention for prediabetes, and against prediabetes as a concept. Conclusions: The majority of ambulatory care pharmacists responding supported all main recommendations related to prediabetes and therefore may be practicable for disseminating diabetes prevention interventions. However, barriers to implementation should be expected.

Statins are widely prescribed, yet statin muscle pain limits their use, leading to increased cardiovascular risk. No validated therapy for statin muscle pain exists. The goal of the study was to assess whether metformin was associated with reduced muscle pain. A secondary analysis of data from the ACCORD trial was performed. An ACCORD sub-study assessed patients for muscle cramps and leg/calve pain while walking, typical non-severe statin muscle pain symptoms. We compared muscle pain between patients using a statin (n = 445) or both a statin and metformin (n = 869) at baseline. Overall patient characteristics were balanced between groups. Unadjusted analysis showed fewer reports of muscle cramps (35%) and leg/calve pain while walking (40%) with statins and metformin compared to statin only (muscle cramps, 42%; leg/calve pain while walking, 47%). Multivariable regression demonstrated a 22% odds reduction for muscle cramps (P = 0.049) and a 29% odds reduction for leg/calve pain while walking (P = 0.01). Metformin appears to reduce the risk of non-severe statin muscle pain and additional research is needed to confirm the findings and assess metformin's impact on statin adherence and related cardiovascular outcomes.

Obesity and diabetes increase hypertensive disorders of pregnancy (HDP) risk, thus preventive interventions are heavily studied. How pregestational prediabetes and related interventions impact HDP risk is less characterized. Therefore, we searched and reviewed the literature to assess the impact on HDP risk of prediabetes and varied interventions. We identified 297 citations related to pregnancy, prediabetes, and early pregnancy interventions. We also reviewed the references and citations of included articles. We included five studies assessing HDP outcomes in women with first trimester hemoglobin A1c in the prediabetes range (5.7–6.4%). One prospective observational study demonstrated first trimester hemoglobin A1c (5.9–6.4%) is associated with increased HDP risk, while another prospective observational study and one retrospective observational study had similar trends without statistical significance. A small and underpowered randomized controlled trial demonstrated initiating gestational diabetes mellitus treatment (i.e., diet, monitoring, ± insulin) in response to first trimester hemoglobin A1c (5.7–6.4%) did not statistically reduce HDP compared with standard care. One retrospective observational study suggested metformin, when started early, may reduce HDP risk in patients with prediabetes. Pregestational prediabetes appears to increase HDP risk. Interventions (i.e., metformin, diet/glucose monitoring, and/or exercise) to reduce HDP risk require additional study with long-term follow-up.

Objective: To review data regarding flibanserin, a recently approved therapy for hypoactive sexual desire disorder (HSDD). Data Sources: Literature search of MEDLINE (September 1995 to November 2015) was performed using the search term flibanserin. Reference lists from included articles were reviewed for pertinent citations. Study Selection and Data Extraction: We included phase-3 trials of flibanserin as a treatment for HSDD. Four reports of phase-3 trials were included. One extension study of four phase-3 trials and one phase-2 pharmacokinetic trial were also included. Data Synthesis: Though a strong placebo response was demonstrated, flibanserin consistently, yet marginally, showed improvement (compared with placebo) in the number of satisfying sexual events per month. The most common adverse events were dizziness (11.4%), somnolence (11.2%), nausea (10.4%), fatigue (9.2%), insomnia (4.9%), and dry mouth (2.4%). Conclusions: Flibanserin is effective in the treatment of HSDD. Flibanserin should be administered at bedtime to limit the risk for hypotension/syncope, accidental injury, and central nervous system (CNS) depression. Concomitant alcohol use contributes to significant CNS depression and hypotension/syncope with flibanserin and should be avoided according to the boxed warning. Careful patient assessment prior to the diagnosis of HSDD and the use of flibanserin is needed for safe use. Prescribing guidelines recommend discontinuing flibanserin at 8 weeks in the absence of benefit. Sexual dysfunction should be addressed in a patient-specific manner. Providers should exercise shared decision making in prescribing flibanserin for HSDD and discuss flibanserin’s benefits and alternative options.

Cardiovascular disease is a leading cause of death in patients with diabetes. Consequently, as antidiabetic medications have demonstrated cardiovascular benefit, cardiologists have been asked to weigh in regarding antidiabetic therapy. The cardiologist's role will continue to grow as antidiabetic agents with cardiovascular benefit are being studied in prediabetes as part of an evolving clinical environment. Still, current guidelines primarily recommend high-intensity lifestyle intervention or metformin for diabetes prevention. Considering that many patients cared for by a cardiologist will have prediabetes, we propose herein that cardiologists can also facilitate diabetes prevention through direct intervention, referring patients to community-based high-intensity lifestyle interventions, and through advocacy, policy, and additional guideline development. The most important messaging for a patient is that avoiding new-onset diabetes can reduce microvascular disease, reduce healthcare cost, and improve health-related quality of life. Moreover, as the mortality risk of patients with a history of myocardial infarction and diabetes is almost double that of patients with a history of myocardial infarction who are free of diabetes, there is even more potential benefit in delaying and/or avoiding diabetes in patients with cardiovascular disease. Despite these important health advantages, the implementation of diabetes prevention strategies is lagging. The under implementation may be exaggerated by published opinions conflicting major guidelines in addition to conflicting guideline recommendations. In conclusion, we propose cardiologists can play a key role in preventing diabetes and aligning practice patterns with guideline recommendations among endocrinology, cardiology, and primary care stake holders.

The 2013 American Heart Association Blood Cholesterol Guidelines increased the number of patients recommended for statin therapy in the United States to 56million. Two common statin side effects are muscle pain, referred to as "statin-associated muscle symptoms", and increased risk for new onset type-2-diabetes mellitus. Up to 25% of statin users report muscle symptoms resulting in many patients being switched to lower dose or lower potency statins, or refusing statins altogether. The most likely signaling mechanisms for statin-associated muscle symptoms overlaps with the proposed mechanism of statin-induced insulin resistance. Metformin has outstanding utility in reducing insulin resistance and preventing type-2-diabetes mellitus, but has not been studied for statin-associated muscle symptom rescue or prevention. The overlapping mechanisms of statin-associated muscle symptoms, statin-induced insulin resistance, and metformin intervention offers the potential to address two common and detrimental side effects of statins. As statins are the single best medication class for preventing cardiovascular events the potential for clinical benefit is large given metabolic syndrome's growing prevalence in the United States. Herein we hypothesize that metformin will rescue and prevent patients from statin-associated muscle symptoms. This hypothesis can benefit two patient groups: 1) patients at risk for diabetes who are taking a statin and experiencing muscle symptoms; and 2) patients with diabetes taking metformin who are to be started on a statin. Method to test Group 1) Symptom Rescue: randomized control trial of metformin versus placebo in patients with prediabetes who are already taking a statin, and are experiencing mild-to-moderate muscle symptoms. Method to test Group 2) Symptom Prevention: meta-analysis, of statin randomized control trials, with patient level data, comparing patients taking metformin at baseline to patients not taking metformin when a statin is started. An efficient method to simulate both symptom rescue and symptom prevention is a skeletal muscle cell culture model of statin-associated muscle symptom markers. These experiments would identify if metformin reverses (rescues) or prevents markers of statin-associated muscle symptoms. As metformin is recommended by the American Diabetes Association for type-2-diabetes mellitus prevention, yet not frequently used, validating this hypothesis will lead towards research and practice change including: a) decreases in the frequency of statin-associated muscle symptoms; leading to subsequent increases in statin therapy compliance; b) increases in metformin use in prediabetes with subsequent decrease in the incidence of type-2-diabetes mellitus; and c) decreases in complications of both cardiovascular disease and diabetes due to improved statin compliance and type-2-diabetes mellitus prevention.

Objectives Diabetes prevention interventions are poorly implemented. While health care costs generally increase, 2 factors affect the relative cost of diabetes prevention interventions: the declining cost of metformin (even without insurance) and the new recommendation for vitamin B12 monitoring during metformin treatment. The study's objective was to update the relative health system cost estimate of metformin for diabetes prevention by incorporating the current health system cost of metformin and the cost of addressing potential metformin-associated vitamin B12 deficiency. The study was designed to assess whether metformin with vitamin B12 supplementation is a cost-saving measure for diabetes prevention and for the updated cost estimate to be useful in assessing future implementation studies. Methods In 2012, the Diabetes Prevention Program Research Group published detailed per capita total direct health system costs for the Diabetes Prevention Program (DPP) and the Diabetes Prevention Program Outcomes Study (DPPOS). The present analysis incorporated the declining cost of metformin and the increasing cost of metformin monitoring into the detailed per capita health system costs found in the DPP and DPPOS. The updated costs were used to assess the total cost of metformin use for diabetes prevention relative to placebo and lifestyle intervention. Results The current health system cost to acquire metformin ranges from $0 to $72 per year. The estimated health system cost to address potential metformin-associated vitamin B12 deficiency is $28 per metformin-treated patient per year. The 10-year total health system cost for metformin in diabetes prevention can decrease by $329 or increase by $21 depending on the cost to acquire metformin. Compared with placebo, the unadjusted cost savings of metformin is generally maintained, although it may double or quadruple depending on how metformin is acquired by patients. Metformin with vitamin B12 supplementation remained less costly and less effective than lifestyle intervention. Conclusion Metformin is generally more cost-saving for diabetes prevention than previously reported because of decreasing costs for patients to acquire metformin. The cost savings was increased despite increased management cost associated with addressing metformin-associated vitamin B12 deficiency.

Doxycycline remains on intermittent shortage. Evidence supports the substitution of minocycline in skin and soft-tissue infections and carefully selected cases of pneumonia. Minocycline may be carefully considered in Lyme disease prophylaxis and Rickettsial disease in the complete absence of doxycycline., Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline's continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable.

Summary Aims The 2012 American College of Chest Physician Evidence-Based Management of Anticoagulant Therapy guidelines suggest an international normalized ratio (INR) testing interval of up to 12 weeks, rather than every 4 weeks, for patients with consistently stable INRs while taking vitamin K antagonists. We aimed to examine the feasibility of extended-interval follow-up in a real-world setting. Methods Patients receiving stable warfarin therapy for ≥12 weeks at baseline began extended-interval follow-up with visits occurring at 6 weeks, 14 weeks, and every 12 weeks thereafter to a maximum of 68 weeks or until they were no longer suitable for extended-interval follow-up. A single INR excursion >0.3 from goal was permitted if a reversible precipitating factor was identified and the INR was expected to return to goal without dose adjustment. The primary outcome was the proportion of patients completing all study follow-up visits. Results Of 48 patients enrolled, 47 had evaluable data. The most common indication for anticoagulation was atrial fibrillation/flutter (53.2%). At baseline, mean prior warfarin treatment duration was 6.7 ± 6 years and median number of weeks on a stable regimen was 24 weeks (IQR, 19–37.5). Eleven patients (23%) completed all study follow-up visits, whereas 17 (36%) did not maintain a stable INR past the 14-week follow-up. Conclusion A large proportion of patients with previously stable (≥3 months) INRs were not able to maintain stable INRs during extended-interval follow-up. More research is needed to identify patient characteristics predictive of success with extended-interval follow-up prior to broad implementation.

Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin–GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.