Advances in the management of type 2 diabetes in adults.

Type 2 diabetes is a chronic and progressive cardiometabolic disorder that affects more than 10% of adults worldwide and is a major cause of morbidity, mortality, disability, and high costs. Over the past decade, the pattern of management of diabetes has shifted from a predominantly glucose centric approach, focused on lowering levels of haemoglobin A1c (HbA1c), to a directed complications centric approach, aimed at preventing short term and long term complications of diabetes, and a pathogenesis centric approach, which looks at the underlying metabolic dysfunction of excess adiposity that both causes and complicates the management of diabetes. In this review, we discuss the latest advances in patient centred care for type 2 diabetes, focusing on drug and non-drug approaches to reducing the risks of complications of diabetes in adults. We also discuss the effects of social determinants of health on the management of diabetes, particularly as they affect the treatment of hyperglycaemia in type 2 diabetes.

Humanistic and Economic Burden of Patients with Cardiorenal Metabolic Conditions: A Systematic Review.

INTRODUCTION: Diabetes is associated with significant economic burden. Moreover, cardiovascular disease (CVD), including heart failure, and chronic kidney disease (CKD) are common comorbidities, leading to premature mortality. We conducted a systematic review to assess the humanistic and economic burden of cardio-renal-metabolic (CRM) conditions in individuals ≥ 18 years with CVD, CKD, and type 2 diabetes mellitus. METHODS: We searched Embase® and Medline® databases from 2011 to January 10, 2022 for English publications reporting humanistic and economic burden outcomes from observational studies, real-world evidence, and economic model studies. Intervention and validation studies were excluded. Study quality was assessed using the Newcastle-Ottawa Scale. Abstracts/posters were identified from four conferences (2020-2022). RESULTS: Of 1804 studies identified, 22 (including four conference publications) were selected involving 351,296,930 participants (one modeled the US population); eight reported healthcare resource utilization (HCRU), seven only cost data, six HCRU and cost data, one reported quality-of-life data (11/18 and 7/18 had estimated low and medium risk of bias, respectively). Participants were predominantly ≥ 65 years and identified as having White ethnicity. Higher costs and HCRU were observed in patients with all three conditions compared to those with two or none. Urban/metropolitan and insured patients had higher healthcare expenditure and service utilization compared to uninsured and racial/ethnic minority populations. Comorbidities were associated with increased hospitalizations, higher costs, and more emergency department visits. In general, patients identified as having Black ethnicity had low odds of using healthcare services, possibly due to disparities in healthcare access and distrust in the system. Limitations included no adjustment for inflation and a predominance of retrospective studies. CONCLUSIONS: This review showed a greater economic burden for patients with CRM conditions, with a clear trend between increasing numbers of comorbidities and increasing healthcare costs/resource use. Comparisons between countries are complicated and the scarcity of evidence from minority racial and ethnic groups and lack of data from non-US geographies warrant further investigation.

Comparison of the Usability, Accuracy, Preference, and Satisfaction of Three Once-Weekly Glucagon-Like Peptide 1 Receptor Agonist Pen Devices in People With Type 2 Diabetes.

Aim: This study's aim was to compare the time and accuracy of use and participants' satisfaction and preferences with pen devices for the once-weekly glucagon-like peptide 1 (GLP-1) receptor agonists dulaglutide, exenatide XR BCise, and semaglutide. Materials and methods: In this triple crossover, open-label, simulated injection study, GLP-1 receptor agonist pen devices were compared, with time and accuracy of use and participants' satisfaction and preferences as primary outcomes. Participants had type 2 diabetes and were naive to GLP-1 receptor agonist therapy. Participants watched instructional videos for each device, demonstrated administration, and then provided feedback after each demonstration. Investigators tracked errors and omissions of demonstration steps for accuracy and time. Differences across devices were compared using univariate mixed models, adjusting for multiple comparisons. Results: Of the 60 participants, 50% were male, a majority (65%) were Caucasian, and most (65%) had adequate health literacy. Participants rated the dulaglutide device easier to use than those of exenatide XR BCise or semaglutide (P <0.001 for each). Participants expressed greater satisfaction with the dulaglutide device compared with those of exenatide XR BCise or semaglutide (P <0.01 for each). Most participants (75%) preferred the dulaglutide device overall; however, many participants (61%) preferred the size and portability of the semaglutide device. The dulaglutide device took less time to use than the exenatide XR BCise or semaglutide devices (69 vs. 126 and 146 seconds, respectively; P <0.001 for each). Participants were less accurate when using the dulaglutide device. Conclusion: Most participants preferred the dulaglutide device. The dulaglutide device took the least amount of time to demonstrate; however, demonstration accuracy was lower.

Tirzepatide: A novel, first-in-class, dual GIP/GLP-1 receptor agonist.

The objective of this article is to review the efficacy and safety of tirzepatide and discuss its potential role in the treatment of type 2 diabetes. Tirzepatide is a novel once-weekly dual GIP and GLP-1 receptor agonist which has been studied in the SURPASS clinical trials in doses of 5 mg, 10 mg, and 15 mg. Tirzepatide phase III clinical trials, SURPASS-1 through SURPASS-5, demonstrate that this medication is safe and effective in treating type 2 diabetes both with and without a variety of background medications versus placebo, semaglutide, insulin degludec, and insulin glargine in different patient populations. Most adverse events were gastrointestinal in nature, with a relatively low withdrawal rate in the active treatment arms. It seems likely that tirzepatide will be recommended as a preferred option in the American Diabetes Association treatment algorithm for high glucose lowering effects in patients with a compelling need for low hypoglycemia risk and weight loss. However, the positioning of tirzepatide in the treatment algorithm will ultimately be dependent on the results of the cardiovascular outcomes trial (CVOT) or other outcome-based trials. Tirzepatide is effective for treating type 2 diabetes by lowering glycated hemoglobin and contributing to significant weight loss.

Taking gambles at face value: Effects of emotional expressions on risky decisions.

Emotional facial expressions are ubiquitous and potent social stimuli that can signal favorable and unfavorable conditions. Previous research demonstrates that emotional expressions influence preference judgments, basic approach-avoidance behaviors, and reward learning. We examined whether emotional expressions can influence decisions such as choices between gambles. Based on theories of affective cue processing, we predicted greater risk taking after positive than negative expressions. This hypothesis was tested in four experiments across tasks that varied in implementation of risks, payoffs, probabilities, and temporal decision requirements. Facial expressions were presented unobtrusively and were uninformative about the choice. In all experiments, the likelihood of a risky choice was greater after exposure to positive versus neutral or negative expressions. Similar effects on risky choice occurred after presentation of different negative expressions (e.g., anger, fear, sadness, and disgust), suggesting involvement of general positive and negative affect systems. These results suggest that incidental emotional cues exert a valence-specific influence of on decisions, which could shape risk-taking behavior in social situations.

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

GLP-1 receptor agonists: an updated review of head-to-head clinical studies.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are attractive options for the treatment of type 2 diabetes (T2D) because they effectively lower A1C and weight while having a low risk of hypoglycemia. Some also have documented cardiovascular benefit. The GLP-1 RA class has grown in the last decade, with several agents available for use in the United States and Europe. Since the efficacy and tolerability, dosing frequency, administration requirements, and cost may vary between agents within the class, each agent may offer unique advantages and disadvantages. Through a review of phase III clinical trials studying dulaglutide, exenatide twice daily, exenatide once weekly, liraglutide, lixisenatide, semaglutide, and oral semaglutide, 14 head-to-head trials were identified that evaluated the safety and efficacy of GLP-1 RA active comparators. The purpose of this review is to provide an analysis of these trials. The GLP-1 RA head-to-head clinical studies have demonstrated that all GLP-1 RA agents are effective therapeutic options at reducing A1C. However, differences exist in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects.

Pharmacologic Approaches to Glycemic Treatment of Type 2 Diabetes: Synopsis of the 2020 American Diabetes Association's Standards of Medical Care in Diabetes Clinical Guideline.

DESCRIPTION: The American Diabetes Association (ADA) updates the Standards of Medical Care in Diabetes annually to provide clinicians, patients, researchers, payers, and other interested parties with evidence-based recommendations for the diagnosis and management of diabetes. METHODS: To develop the 2020 Standards, the ADA Professional Practice Committee, comprising physicians, adult and pediatric endocrinologists, diabetes educators, registered dietitians, epidemiologists, pharmacists, and public health experts, continuously searched MEDLINE (English language only) from 15 October 2018 through August-September 2019 for pertinent studies, including high-quality trials that addressed pharmacologic management of type 2 diabetes. The committee selected and reviewed the studies, developed the recommendations, and solicited feedback from the larger clinical community. RECOMMENDATIONS: This synopsis focuses on guidance relating to the pharmacologic treatment of adults with type 2 diabetes. Recommendations address oral and noninsulin injectable therapies, insulin treatment, and combination injectable therapies. Results of recent large trials with cardiovascular and renal outcomes are emphasized.

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes.

WHAT IS KNOWN AND OBJECTIVE: In recent years, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) including once-weekly (QW) formulations have been incorporated into type 2 diabetes (T2D) clinical guidelines, making it essential that pharmacists and healthcare professionals (HCPs) have a clear understanding of their safety profiles. Currently, three QW GLP-1 RAs are approved and marketed in the United States for the treatment of T2D: dulaglutide, exenatide extended-release and semaglutide. This review provides pharmacists and HCPs with collated data related to potential safety and tolerability issues when patients use QW GLP-1 RAs, enabling patient education and treatment optimization. METHODS: This is a narrative review comparing the safety and tolerability of the three QW GLP-1 RAs, using data from Phase 3 clinical trials. Extracted safety data included gastrointestinal (GI) adverse events (AEs), hypoglycaemia, injection-site reactions, pancreatitis, neoplasms, gallbladder events, and diabetic retinopathy (DR) and/or its complications (DRCs). RESULTS AND DISCUSSION: A total of 30 trials were identified for inclusion; eight were head-to-head trials involving another GLP-1 RA; of these, six compared GLP-1 RAs with different dosing regimens (QW vs once-daily or twice-daily), and two were direct QW vs QW GLP-1 RA comparisons. The most commonly reported AEs were GI events (notably nausea, vomiting and diarrhoea), but there was variation between the three QW drugs. These were generally mild-to-moderate in severity and transient. Risk of hypoglycaemia, injection-site reactions, pancreatitis, neoplasms and gallbladder events was generally low across the GLP-1 RAs investigated. Overall rates of DR or DRC were low across the trials. Only in one trial (SUSTAIN 6) there were significantly more DRC events reported in patients treated with QW semaglutide (3.0%) compared with placebo (1.8%). This was likely due to the rapid improvement in glucose control in patients with pre-existing DR enrolled within that trial. WHAT IS NEW AND CONCLUSION: This review puts the latest clinical data from the marketed QW GLP-1 RAs into context with results from older Phase 3 trials, to enable pharmacists and HCPs to make informed treatment decisions. Each of the three QW GLP-1 RAs has their own safety profile, which should be considered when choosing the optimal treatment for patients.

Student perceptions of the utility of the Pharmacy Curriculum Outcomes Assessment.

INTRODUCTION: This study assessed student perceptions, preparation, and result use strategies of the Pharmacy Curriculum Outcomes Assessment (PCOA). Secondarily, it studied the effect of schools/colleges of pharmacy (S/COP) PCOA management on student perceptions. METHODS: A 52-item electronic questionnaire assessed PCOA preparation of final year students, review/use of results, remediation participation, self-reported motivation, and perceptions of the exam's ability to measure PCOA blueprint areas and North American Pharmacy Licensure Examination (NAPLEX)/advanced pharmacy practice experience (APPE) readiness. Programs were given a questionnaire to determine their PCOA practices. RESULTS: The student survey was completed by 341 students (40% response rate). Students prepared very little for the PCOA and few reported participation in PCOA-based remediation (6%). Students perceived the PCOA to measure the four domains moderately well, although administrative sciences were significantly lower. Students reported less confidence in the exam's ability to measure APPE/NAPLEX-readiness. Although few used the PCOA to guide their NAPLEX preparation (18%), they were more likely to do so than for APPEs (4%). Students reported a higher perceived increase in motivation if PCOA results were connected to APPE placement, remediation, and progression as opposed to prizes, rewards, or other recognitions. CONCLUSION: This is the first multi-institutional study to review student perceptions about the PCOA. These data can be used along with other PCOA data to help schools develop incentive, remediation, and examination administration procedures depending on the programs desired use for the PCOA exam.

Intranasal Glucagon: A New Way to Treat Hypoglycemic Emergencies.

Objective: To review the safety, efficacy, and administration of intranasal (IN) glucagon for the management of hypoglycemia. Data Source: A literature search of PubMed/MEDLINE (1995 to November 2019) using the terms intranasal glucagon, nasal glucagon, glucagon, hypoglycemia treatment, and hypoglycemia management was completed. Study Selection and Data Extraction: English-language studies evaluating IN glucagon were evaluated. Data Synthesis: IN glucagon is a newly approved product for the treatment of hypoglycemia in patients with diabetes, 4 years and older. Administered as a 3-mg dose, it was shown to be noninferior to intramuscular (IM) glucagon. In comparison trials, more than 98% of hypoglycemic events were treated successfully with IN glucagon in both pediatric and adult patients. In simulated and real-world studies, IN glucagon was administered in less than a minute for the majority of scenarios. IM glucagon took longer to administer, ranging from 1 to 4 minutes, and often, patients did not receive the intended full dose. Nausea and vomiting, known adverse events for glucagon, as well as local adverse events were most commonly reported with IN glucagon. Relevance to Patient Care and Clinical Practice: IN glucagon is safe, effective, easy to use, and does not require reconstitution prior to use, which can lead to faster delivery in a severe hypoglycemic event. It does not require age- or weight-based dosing. This delivery method offers an option for someone who fears needles or is uncomfortable with injections. Conclusion: IN glucagon is a safe, effective, easy to use, needle-free treatment option for severe hypoglycemia.

Oral semaglutide in type 2 diabetes.

BACKGROUND: Previously, the only available glucagon-like peptide-1 receptor agonists (GLP-1 RA) were injectable. Approval of oral semaglutide (Rybelsus®) represents the first orally available GLP-1 RA. OBJECTIVE: To review the literature and describe pharmacologic, pharmacokinetic, and pharmacodynamics properties; clinical safety; and efficacy of oral semaglutide, a newly approved oral GLP-1 RA. METHODS: A MEDLINE (1995-October 2019) and ClinicalTrials.gov search was conducted using the terms oral semaglutide, semaglutide, PIONEER, and a combination of those terms. Reference citations from publications identified were also reviewed. All English-language studies, including abstracts, evaluating oral semaglutide use in humans were included in this review. CONCLUSIONS: The approval of oral semaglutide (Rybelsus®) represents a paradigm shift in the management of T2D as this is the first FDA-approved oral GLP-1 RA. Oral semaglutide may be an attractive option for patients with T2D who require improved glycemic control, would like to lose weight, and who are not interested in injectable therapy. However, the lack of positive cardiovascular (CV) and renal data are significant limitations to its use.

A review of sotagliflozin for use in type 1 diabetes.

Type 1 diabetes is a challenging disease that is largely managed with the use of insulin. The risk of hypoglycemia, side effects of weight gain, and high glucose variability associated with insulin use have prompted researchers to explore additional therapies to treat this condition. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of medications that lower glucose in type 2 diabetes patients independent of insulin action, and have been studied for use in the type 1 diabetes population. Sotagliflozin is an SGLT2 inhibitor that demonstrates a unique binding affinity for the SGLT1 receptor. A total of three phase III clinical trials (inTandem1, inTandem2, and inTandem3) were conducted to evaluate the safety and efficacy of sotagliflozin in type 1 diabetes. A modest hemoglobin A1C reduction of 0.3-0.4% was observed, with secondary benefits of reduced glucose variability, reduced insulin dosage, and positive weight loss effects. Overall there was a reduction in the risk of severe hypoglycemia with sotagliflozin, but a higher rate of ketone formation and risk of diabetic ketoacidosis was observed, along with increased mycotic infections and volume depletion effects.

Effects of Diabetes Numeracy on Glycemic Control and Diabetes Self-Management Behaviors in Patients on Insulin Pump Therapy.

INTRODUCTION: Diabetes numeracy (DN) skills are crucial in patients on insulin pump therapy. Little evidence exists regarding DN in this patient population. METHODS: This exploratory, observational, cross-sectional study assessed the DN levels of patients on insulin pump therapy and potential relationships with glycemic control and self-management behaviors. Seventy-two patients on insulin pump therapy were recruited from one specialty endocrinology clinic. Subjects completed validated tools to measure DN [Diabetes Numeracy Test (DNT-15)] and self-management behaviors [Diabetes Self-Management Questionnaire (DSMQ)]. A general diabetes questionnaire assessed socioeconomic information and self-efficacy. Additional self-management behaviors and glycemic control data were collected from patients' medical records. Patients were categorized into two groups based on DNT-15 scores to explore potential relationships between DN scores and patient characteristics, glycemic control, and self-management behaviors. RESULTS: Average age was 52 ± 15 years, glycosylated hemoglobin (A1C) was 7.7% ± 1.2% (61 mmol/mol), duration of diabetes was 28 ± 15 years, and duration of pump use was 3.4 ± 1.3 years. The average DNT-15 score was 87.5% ± 18%. Forty-three participants (60%) scored ≥ 90% and 29 participants (40%) scored < 90%. Eighteen percent were unable to calculate the carbohydrate content from a nutrition label. Participants with lower DNT-15 scores had higher A1C levels (8.0% vs. 7.5%, p = 0.04), were older (58.3 vs. 47.7, p = 0.003), were more likely to describe their diabetes self-care as poor (p = 0.04), and were less confident in using their pump features (p = 0.02) than those with higher DNT-15 scores. CONCLUSION: Many patients on insulin pump therapy have deficiencies with DN which may be associated with older age and higher A1C levels.

Appropriate Titration of Basal Insulin in Type 2 Diabetes and the Potential Role of the Pharmacist.

A substantial proportion of patients with suboptimal control of their type 2 diabetes experience delays in treatment intensification. Additionally, patients often experience overuse of basal insulin, commonly referred to as "over-basalization," whereby basal insulin continues to be uptitrated in order to meet targets, when addition of a mealtime bolus insulin dose may be a more appropriate option. In order to overcome these challenges, there is a need to develop the capacity of allied healthcare professionals to provide appropriate support to these patients, such as during initiation or titration of basal insulin. Pharmacists play an integral role in healthcare delivery, with patients seeing their pharmacist, on average, seven times more often than their primary care physician. This places pharmacists in a unique position to provide diabetes education and care, which may help patients avoid clinical inertia. Nevertheless, the management of the disease with basal insulin is becoming increasingly complex, with growing numbers of treatment options (such as recent second-generation longer-acting basal insulin formulations) and frequently updated titration algorithms. The two most common titration schedules specify either increasing doses by a set amount every 2-3 days or a treat-to-target strategy. Neither schedule has been shown to be superior, and the decision to use one or the other should be based on a discussion between the clinician and patient after assessment of mental and physical acumen, comfort of both parties, and follow-up plans. This review article discusses basal insulin therapy options and titration algorithms from the unique perspective of the pharmacist in order to help ensure that optimal antidiabetes therapy is initiated, appropriately titrated, and maintained.Funding: Sanofi US, Inc.

5-alpha-dihydrotestosterone elevations associated with phentermine use.

BACKGROUND: A case of 5-alpha-dihydrotestosterone (DHT) elevation associated with phentermine initiation is reported, and possible mechanisms are discussed. There are no published reports of this association in the literature. METHODS: Clinical and laboratory information is described. RESULTS: A 72-year-old male with metastatic prostate cancer taking dutasteride to lower his DHT levels initiated phentermine 15 mg daily for weight loss. His DHT level drawn within 1 week prior to starting phentermine was 9.9 pg/ml. When reporting for follow up 2 weeks later, his DHT level had increased to 114 pg/ml. The DHT level was checked again 2 weeks after that visit, and had increased to 174 pg/ml. At that time, phentermine was discontinued, and 1 week later, the DHT level had decreased to 20.1 pg/ml. Over the next 4 months, the patient's DHT levels were maintained at less than 20 pg/ml. Phentermine 15 mg daily was then reinitiated while his DHT level was 7.5 pg/ml. Two weeks after resuming phentermine, his DHT level had again increased to 196 pg/ml. The patient's phentermine was then discontinued, and around 1 week later, his DHT level had fallen to 5.1 pg/ml. CONCLUSION: A 72-year-old male with metastatic prostate cancer experienced profound increases in DHT upon initiation of phentermine despite continuation of his baseline dutasteride therapy. The etiology of these increases is still unclear.

Semaglutide: The Newest Once-Weekly GLP-1 RA for Type 2 Diabetes.

OBJECTIVE: To review efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide for type 2 diabetes (T2D). DATA SOURCES: A literature search of PubMed/MEDLINE and EMBASE using the term semaglutide was completed through April 2018. A search of clinicaltrials.gov was also conducted. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the efficacy and/or safety of semaglutide were evaluated. DATA SYNTHESIS: Semaglutide is a newly approved GLP-1 RA for the treatment of T2D. Administered once weekly at a dose of 0.5 or 1 mg, it has been compared with placebo, sitagliptin, insulin glargine, a combination of oral antidiabetic therapies, and 2 GLP-1 RAs, exenatide ER and dulaglutide, and demonstrated greater efficacy compared with these therapies. Published data from studies ranging from 30 to 104 weeks duration demonstrate efficacy with decreases in hemoglobin A1C (A1C) ranging from 1.1% to 2.2%. Studies show reductions in weight from 1.4 to 6.5 kg. Semaglutide demonstrated a reduction in the composite outcome of cardiovascular (CV) death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo in patients at high risk of CV events (hazard ratio = 0.74; P = 0.02). Common adverse effects include nausea, vomiting, and diarrhea as seen with other GLP-1 RAs. Relevance to Patient Care and Clinical Practice: Semaglutide represents an attractive GLP-1 RA considering its A1C and weight reduction. It provides patient convenience and high patient satisfaction. CONCLUSIONS: Semaglutide is an appealing option for the treatment of T2D as a once-weekly GLP-1 RA with established glycemic, CV, and weight benefits.