Real-world evaluation of the effects of tirzepatide in patients with type 2 diabetes mellitus.

AIMS: Tirzepatide is a first-in-class combination glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP1-RA) approved for treatment of adults with type 2 diabetes mellitus (T2DM) and chronic weight management. The aim of this analysis was to assess the real-world efficacy of tirzepatide in patients with T2DM. METHODS: This retrospective observational study evaluated patients with T2DM from a large urban academic medical centre who received at least 3 months of continuous tirzepatide treatment. The primary outcome was change in A1C from following tirzepatide treatment. Secondary outcomes included change in body weight and body mass index (BMI) after tirzepatide was initiated. RESULTS: A total of 1896 patient charts were reviewed, and 612 patients were evaluated for the primary outcome. Over a median time period of 10.4 months, treatment with tirzepatide resulted in a mean A1C reduction of 1.02 ± 1.48% (p < 0.001). A total of 570 patients were evaluated for the secondary outcomes. Tirzepatide was associated with a mean reduction in body weight of 7.3 ± 9.3 kg (p < 0.001) and a mean reduction in BMI of 2.5 kg/m2. Greater A1C lowering and weight loss was observed in patients without prior GLP1-RA treatment compared to those switched to tirzepatide from GLP1-RA. CONCLUSIONS: In a real-world population of US patients with T2DM, tirzepatide was associated with clinically and statistically significant reductions in A1C and body weight. Greater reductions in both A1C and body weight were observed among patients who were GLP1-RA naïve compared to patients switched from GLP1-RA to tirzepatide.

Polypharmacy and Potentially Inappropriate Medication Use in Older Blacks with Diabetes Mellitus Presenting to the Emergency Department.

Background: Medication-related problems in older Blacks with diabetes mellitus (DM) are not well established. Objectives: To describe the frequency of medication-related problems in older Blacks with DM presenting to the emergency department (ED). Methods: The study was a cross-sectional analysis of baseline data from a randomized controlled trial evaluating Blacks aged ≥60 years of age presenting to the ED. Polypharmacy, potentially inappropriate medication (PIM) use, and anticholinergic score were evaluated. Results: Of 168 patients (median age = 68, range 60-92), most (n = 164, 98%) were taking ≥5 medications, and 67 (39.9%) were taking a PIM. A majority (n = 124, 74%) were taking a medication with an anticholinergic score ≥1. Number of medications was correlated with number of PIMs (r = .22, p = .004) and anticholinergic score (r = .50, p < .001). Conclusion: Polypharmacy and PIM use was common in older Blacks with DM.

The Role of PCSK9 Inhibitors in the Treatment of Hypercholesterolemia.

OBJECTIVE: To evaluate the efficacy, safety, and cost-effectiveness of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and describe its place in therapy for the treatment of hypercholesterolemia. DATA SOURCES: A search of MEDLINE, CINAHL, and Clinicaltrials.gov was performed from January 2012 to March 2018 to identify literature pertaining to PCSK9 inhibitors using pre-specified search terms. Additional references were identified from citations of the literature. STUDY SELECTION AND DATA EXTRACTION: Only articles in English were reviewed. Phase II, phase III, pooled, post hoc, and cardiovascular (CV) trials were included. Cost-effectiveness studies and conference materials were also reviewed. DATA SYNTHESIS: All trials evaluating alirocumab and evolocumab demonstrated significant low-density lipoprotein cholesterol (LDL-C) lowering versus comparators. Two trials revealed a decrease in the major adverse cardiovascular events (MACE) end point with PCSK9 inhibitor use; 1 of these 2 trials revealed a decrease in all-cause mortality with alirocumab use. No significant safety concerns apart from injection site reactions were noted. Despite these results, 4 cost-effectiveness analyses failed to meet acceptable thresholds. Relevance to Patient Care and Clinical Practice: This review describes the most up-to-date evidence regarding PCSK9 inhibitors. A discussion on LDL-C lowering potential, effect on CV events and mortality, safety considerations, feasibility of administration, and cost are included to guide clinicians on future use. CONCLUSION: The PCSK9 inhibitor drug class is an effective LDL-C lowering option for patients with the highest risk of CVD events and high LDL-C despite the use of statin therapy. For more widespread use, significant cost reductions are needed.

Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies.

Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi-Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management.

Management of prediabetes: a comparison of the treatment approaches utilized by a family practice clinic and an internal medicine/endocrinology practice.

PURPOSE: To compare the management of prediabetes between a family practice clinic and internal medicine/endocrinology practice. METHODS: A randomized, retrospective evaluation of the medical history in 168 eligible patients with a diagnosis of prediabetes or abnormal blood glucose (BG) at a family practice clinic (n = 78) and an internal medicine/endocrinology practice (n = 90). RESULTS: The internal medicine/endocrinology practice provided more counseling regarding lifestyle modifications (91.1% vs 76.9%, P = .039), specific physical activity recommendations (26.7% vs 7.7%, P = .003), and recommended more patients receive 150 minutes/week of moderate exercise (8.9% vs 1.3%, P = .038). The family practice clinic provided more written dietary information (16.9% vs 13.3%, P = .044) and specific weight loss goals (20.5% vs 6.7%, P = .015). The internal medicine/endocrinology practice initiated pharmacological therapy in more patients (51.1% vs 3.8%, P< .001) and had a significant decrease in fasting BG from baseline compared to the family practice clinic (-9.0 vs -5.6 mg/dL, P< .001). CONCLUSION: Providers are likely to initiate nonpharmacological therapy but may not provide specific education recommended by the American Diabetes Association. The integration of a multidisciplinary team to provide guideline-based nonpharmacologic counseling may be beneficial in improving outcomes in the management of prediabetes.