Evaluating real world clinical response of once weekly subcutaneous semaglutide and its daily oral formulation for the treatment of type 2 diabetes in primary care practice

Objective: Semaglutide is the first glucagon-like peptide- 1 receptor agonist with oral and subcutaneous formulations. We studied patient adherence and clinical response following their prescription in a primary care setting. Method(s): We searched for patients starting semaglutide between October 2020 to November 2021 in primary care registries in Dudley, West Midlands. We tracked their collection of medications for up to six months, changes in HbA1C and weight if these data were available at 26 weeks (range 22-52 weeks), with significance tested using a t-test. Patients prescribed both formulations were excluded. Result(s): Clinical data were available in 180 of the 443 patients. Baseline HbA1c was 79.0 +/- 18.6mmol/mol (Ozempic) and 81.9 +/- 19.3mmol/mol (Rybelsus) and pre-treatment weight was 108.4 +/- 10.5 kg (Ozempic) and 104.3 +/- 26.7 kg (Rybelsus). 62.8% of patients were of non-white ethnicity and 82.8% were on >= two anti-diabetic drugs. In patients with six-month follow-up data, mean reduction in HbA1c and weight was 17.1 +/- 20.8mmol/ mol and 3.9 +/- 6.2 kg (Ozempic n = 53, p < 0.01) and 18.2 +/- 14.5mmol/mol and 5.9 +/- 4.2 kg (Rybelsus n = 5, p < 0.05). Drug continuation rates were measured in 324 patients. 3.2% and 19.0% of patients for Ozempic and Rybelsus respectively did not obtain further prescriptions after their initial script. At six months, 87.2% continued with Ozempic and 57.2% with Rybelsus. Conclusion(s): This study demonstrates similarly significant reductions in HbA1c and weight with Ozempic and Rybelsus, despite the complexity of follow-up during Covid-19 restrictions. The lower adherence to Rybelsus warrants further study.

Impact of COVID-19 Lockdown on Anthropometric Body Measurements and Nutritional Behaviors in a Colombian Cohort Receiving Online Nutritional Advice

Objective: In this study, we aimed to retrospectively assess the change in weight before and after the COVID-19 mandatory lockdown in Colombia among adults who received nutritional and healthy lifestyle recommendations at weight loss and wellness clinics by telehealth. The primary objective was to describe and compare the mean weight reduction measured at the baseline and by the end of the lockdown. Secondary objectives include describing and comparing body fat percentage, muscle mass percentage, and BMI measured at the baseline and by the end of the lockdown. Method(s): One hundred and seventy-two middle-aged (18-68 years old) women and men received online nutritional and healthy lifestyle advice during the COVID-19 lockdown in Colombia. Weight, fat (%), muscle mass (%), and BMI were assessed before and after the lockdown. We included baseline measurements taken before the lockdown from March 1st to June 20th, 2020, and post-lockdown measurements from August 31st to October 20th, 2020. Exclusion criteria included pregnancy or breastfeeding women, acutely decompensated diabetes, hypertension, CKD, Hypothyroidism or taking any of the obesity treatment medications approved in Colombia, including liraglutide, semaglutide or orlistat. A retrospective analysis was completed to compare the change in mean body anthropometrics. Shapiro Wilk test was used to assess for normality. Paired T Test and Wilcoxon sign test were used to compare the distribution of body anthropometrics before and after the lockdown. IRB approval was obtained before exporting and analyzing the collection of data. Result(s): Out of 205 subjects and after a review of exclusion criteria, 172 subjects were included in the data analysis. 90.1% (155) were women. 52.3% (135) had overweight or obesity. After the COVID-19 lockdown, the mean weight loss reduction was 8.79 kg (SD +/- 5.45, p<0.0001), corresponding to an 11.4% weight loss reduction. The mean fat mass percentage loss was 2.89 % (SD +/- 2.64, p<0.0001), and the mean BMI presented a reduction of 3.16 (SD +/- 1.96, p <0.0001). The mean muscle percentage loss was 0.10% (SD +/- 2.67, p 0.482). Discussion/Conclusion: Subjects receiving telehealth nutritional advice in Colombia during the COVID-19 lockdown had significant clinical and statistical weight, BMI, and fat loss reduction. Muscle mass was preserved;however, this mean change was not statistically significant. Physical inactivity during the lockdown period was a potential contributor to a nonsignificant mean muscle mass change. The subjects in this study were highly motivated to virtually attend weight loss and wellness clinics and to improve body anthropometrics by optimizing lifestyle changes. Telehealth weight loss strategies should always be considered when in-person patient interaction is not available.Copyright © 2023

Adipose tissue, systematic inflammation, and neurodegenerative diseases

Obesity is associated with several diseases, including mental health. Adipose tissue is distributed around the internal organs, acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues. Excessive nutritional intake results in hypertrophy and proliferation of adipocytes, leading to local hypoxia in adipose tissue and changes in these adipokine releases. This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines. The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling, which can generate a neuroinflammatory process. In this review, we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction. We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain, particularly the hypothalamus and hippocampus, and that this is partially responsible for these negative cognitive outcomes. In addition, we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.Copyright © 2023 Wolters Kluwer Medknow Publications. All rights reserved.

Tirzepatide (Mounjaro) for Type 2 Diabetes

The FDA has approved tirzepatide (Mounjaro - Lilly), a peptide hormone with activity at both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, to improve glycemic control in adults with type 2 diabetes. Tirzepatide, which is injected subcutaneously once weekly, is the fi rst dual GIP/GLP-1 receptor agonist to become available in the US. Selective GIP receptor agonists are not available in the US;GLP-1 receptor agonists have been available for years. Copyright © 2022, Medical Letter Inc.. All rights reserved.

An Unusual Case of Autoantibody-Negative KetosisProne Diabetes (KPD) Secondary to Marked Insulin Resistance

KPD is classically regarded as an atypical form of diabetes caused by near-complete beta-cell failure. A 37-year-old Egyptian man (BMI: 27.7 Kg/m2) presented with hyperglycemia (362 mg/dL) and DKA (arterial pH 7.20, ketonemia 5.0 mmol/L, ketonuria 80 mg/dL) . He was afebrile, with recent polyuria, polydipsia and weight loss. HbA1c was 107 mmol/mol (11.9%) and blood tests excluded diabetes secondary to endocrinopathies. SARS-CoV-2 RT-PCR test was negative. IV insulin infusion (0.1 IU/kg/h) and IV fluid therapy were started. He was shortly transitioned to a sc basal-bolus insulin regimen (0.7 IU/kg/day) . Mixed-meal tolerance test (MMTT) revealed a peak 120-min stimulated C-peptide of 12.3 ng/mL, suggesting marked insulin resistance. Islet autoantibodies (ICA, IAA, GADA, IA-2A, ZnT8A) and insulin receptor autoantibodies (IgG/IgM) were negative. HLA genotyping detected the following haplotypes: DRB1∗01, ∗04;DQA1∗01:01P, ∗03:01P;DQB1∗03:02P, ∗05:01P. Insulin dose was gradually reduced and insulin therapy was discontinued after 4 months in favor of metformin (2550 mg/day) plus sc semaglutide (up to 1 mg/week) . After one year, MMTT revealed a peak 60-min stimulated C-peptide of 8.25 ng/mL. During the 18-month follow-up period, fasting capillary beta-hydroxybutyrate values were <0.2 mmol/L and HbA1c remained <48 mmol/mol (<6.5%) , indicating disease remission. This case suggests the existence of an autoantibody-negative KPD subtype driven by marked insulin resistance rather than by insulinopenia.

Efficacy of subcutaneous semaglutide compared to placebo for weight loss in obese, non-diabetic adults: a systematic review & meta-analysis.

BACKGROUND: Research on semaglutide's effect on weight loss has been largely focused on Type 2 Diabetics. No meta-analyses of semaglutide's efficacy in non-diabetic individuals have been conducted to date. Expanding the knowledge of semaglutide's outcome in non-diabetics may provide impactful changes at the clinical level. AIM: This systematic review and meta-analysis quantified the efficacy of subcutaneous semaglutide in treating obesity in non-diabetic adult patients compared to placebo. METHOD: Academic Search Premier, Cumulative Index to Nursing and Allied Health Literature (CINAHL) complete, MEDLINE with Full Text, Cochrane Central Register of Controlled Trials, medrxiv.org, and clinicaltrials.gov were systematically investigated using a predetermined search strategy from inception to August 21, 2021. Covidence.org was used to screen, select, and extract data by two independent reviewers. Individual study bias was assessed using the Cochrane Risk of Bias 2 tool. Data were exported to RevMan v5.4, where meta-analysis was conducted using a DerSimonian and Laird random-effects model. RESULTS: The initial search identified 332 relevant articles and ultimately retained four randomized controlled trials encompassing 2,882 participants with a BMI ≥ 27 kg/m2. Patients treated with semaglutide experienced a clinically significant reduction in mean body weight - 11.62 kg (95% CI: -13.03 to -10.21; P < 0.00001). CONCLUSION: This systematic review and meta-analysis validates the clinical efficacy of semaglutide for the treatment of obesity in the adult, non-diabetic population.

Meeting the Challenge of Virtual Diabetes Care: A Consensus Viewpoint on the Positioning and Value of Oral Semaglutide in Routine Clinical Practice.

While glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, are among the most effective drugs for treating people with type 2 diabetes (T2D), they are clinically under-utilised. Until recently, the only route for semaglutide administration was via subcutaneous injection. However, an oral formulation of semaglutide was recently licensed, with the potential to address therapy inertia and increase patient adherence to treatment, which is essential in controlling blood glucose and reducing complications. The availability of oral semaglutide provides a new option for both clinicians and patients who are reluctant to use an injectable agent. This has been of particular importance in addressing the challenge of virtual diabetes care during the COVID-19 pandemic, circumventing the logistical problems that are often associated with subcutaneous medication administration. However, there remains limited awareness of the clinical and economic value of oral semaglutide in routine clinical practice. In this article, we present our consensus opinion on the role of oral semaglutide in routine clinical practice and discuss its value in reducing the burden of delivering diabetes care in the post-COVID-19 pandemic period of chronic disease management.

Weight loss outcomes with telemedicine during COVID-19

Background: Amidst the COVID-19 pandemic, telemedicine was a strategy to expand patient care during quarantine. However, there is little data on how this transition may have impacted weight loss outcomes and practices among patients with overweight/obesity. Methods: This retrospective observational study of adults who established care at the Weill Cornell Comprehensive Weight Control Center during September-November 2019 and May-July 2020 explored weight loss outcomes and weight management practices over 6 months of follow-up. Results: Of 516 charts eligible for review, 245 (47.5%) were included for analysis after excluding patients who failed to return for a follow-up visit within 6 ± 3 months or who were missing relevant data. Of 245 patients, 69 had in-person visits only ('in-person'), 91 had video visits only ('video'), and 85 started in-person and later switched to video visits ('hybrid'). All cohorts were predominantly white and female. Median ages were 56, 49, and 49 years, and baseline median weights were 98.9, 96.8, and 93.0kg for in-person, video, and hybrid cohorts, respectively. The median percent weight losses were not significantly different among cohorts: 4.3% [-8.5, -1.5] in the in-person cohort, 5.8% [-9.7, -2.4] in the video cohort, and 5.7% [-8.7, -2.2] in the hybrid group. The percent of patients who achieved ≥5% weight loss were also similar: 46.4%, 59.3%, and 55.3%, respectively. The median number of visits were 4 [3,4] for the in-person cohort, 4 [3,6] for the hybrid cohort, and 5 [4,7] for the video visit cohort. Median number of anti-obesity medications (AOMs) prescribed was 1 [1,2] for the in-person cohort and 2 [1, 2] for both the hybrid and video cohorts. The most common AOMs were metformin (all cohorts) followed by semaglutide (in-person and video) or topiramate (hybrid). Conclusions: Video visits are an effective weight management strategy and require further exploration to compare to in-person care.

Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes.

Semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, is available as monotherapy in both subcutaneous as well as oral dosage form (first approved oral GLP-1 receptor agonist). It has been approved as a second line treatment option for better glycaemic control in type 2 diabetes and currently under scrutiny for anti-obesity purpose. Semaglutide has been proved to be safe in adults and elderly patients with renal or hepatic disorders demanding no dose modification. Cardiovascular (CV) outcome trials established that it can reduce various CV risk factors in patients with established CV disorders. Semaglutide is well tolerated with no risk of hypoglycaemia in monotherapy but suffers from gastrointestinal adverse effects. A large population affected with COVID-19 infection were diabetic; therefore use of semaglutide in diabetes as well as CV patients would be very much supportive in maintaining health care system during this pandemic situation. Hence, this peptidic drug can be truly considered as a quintessential of GLP-1 agonists for management of type 2 diabetes.

Real-World Use of Once-Weekly Semaglutide in Type 2 Diabetes: Results from the SURE UK Multicentre, Prospective, Observational Study.

INTRODUCTION: Once-weekly (OW) semaglutide was associated with clinically relevant improvements in glycaemic control and body weight versus comparators in the SUSTAIN randomised controlled trials (RCTs). SURE UK, which is one of a series of individual studies that comprise the SURE programme, evaluated the use of OW semaglutide in a real-world patient population with type 2 diabetes (T2D) in the UK. METHODS: In this prospective, observational study, adults (≥ 18 years) with ≥ 1 documented glycated haemoglobin (HbA1c) value ≤ 12 weeks before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~ 30 weeks, although due to the COVID-19 pandemic, visits up to week 52 were permitted). Secondary endpoints included change in body weight, waist circumference and patient-reported outcomes (PROs). Physicians were to report all episodes of documented or severe hypoglycaemia, fatal events, serious adverse drug reactions, pregnancies and adverse events (AEs) in foetuses/newborn infants; other AEs during the study period could be reported on a voluntary basis. RESULT: The estimated mean change in HbA1c from baseline to EOS was - 16.3 mmol/mol [95% confidence interval (CI): - 18.22, - 14.37] (- 1.5%-points [95% CI - 1.67, - 1.31]; p < 0.0001) among the 171 enrolled patients who completed the study on treatment. Mean body weight change was - 5.8 kg (95% CI - 6.75, - 4.94; p < 0.0001). Sensitivity analyses showed similar results. Improvements were also observed in other secondary endpoints, including PROs. No new safety concerns were identified with semaglutide treatment. CONCLUSION: Patients receiving OW semaglutide experienced statistically significant and clinically relevant reductions from baseline in HbA1c and body weight. These results are in line with those of the SUSTAIN RCTs and support the use of OW semaglutide in routine clinical practice in adults with T2D in the UK. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03876015.