Injectable Glucagon-like Peptide-1 Research Articles

The long-term cost-effectiveness of oral semaglutide versus empagliflozin and dulaglutide in Portugal

BackgroundOral semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog that has been associated with improvements in glycated hemoglobin (HbA1c) and body weight versus sodium-glucose cotransporter-2 inhibitor empagliflozin and injectable GLP-1 receptor agonist dulaglutide in the PIONEER 2 clinical trial and in a recent network meta-analysis (NMA), respectively. The aim of the present study was to evaluate the long-term cost-effectiveness of oral semaglutide 14 mg versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes from a healthcare payer perspective in Portugal.MethodsIn two separate analyses, outcomes were projected over patients’ lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 4% per annum. Clinical data were sourced from the PIONEER 2 trial and the NMA for the comparisons versus empagliflozin and dulaglutide, respectively. Patients were assumed to receive initial therapies until HbA1c exceeded 7.5%, then treatment-intensified to solely basal insulin therapy. Costs were accounted from a National Healthcare Service perspective in Portugal and expressed in 2021 euros (EUR). Utilities were taken from published sources.ResultsOral semaglutide 14 mg was associated with improvements in life expectancy of 0.10 and 0.03 years, and quality-adjusted life expectancy of 0.11 and 0.03 quality-adjusted life years (QALYs), versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively. Improved clinical outcomes were due to a reduced cumulative incidence and increased time to onset of diabetes-related complications with oral semaglutide. Total costs were projected to be EUR 2548 and EUR 814 higher with oral semaglutide versus empagliflozin and dulaglutide, with higher acquisition costs partially offset by cost savings from avoidance of diabetes-related complications. Oral semaglutide 14 mg was therefore associated with incremental cost-effectiveness ratios of EUR 23,571 and EUR 23,927 per QALY gained versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively.ConclusionsBased on a willingness-to-pay threshold of EUR 30,000 per QALY gained, oral semaglutide 14 mg was considered cost-effective versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes in Portugal.

POSC359 The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide & Liraglutide in Type 2 Diabetes Patients (TROPHIES): Patient Reported Outcomes at 12-Months

Patient-reported outcome (PRO) measures provide information that complement clinical data. Studies assessing PRO measures in people living with T2D who initiate injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) medication in routine clinical practice are limited. To better understand the perspectives of people living with T2D regarding their overall health, treatment/device satisfaction, and quality of life and work, here we describe perspectives of participants at the 12-month time-point of TROPHIES.

Higher Rates of Persistence and Adherence in Patients with Type 2 Diabetes Initiating Once-Weekly vs Daily Injectable Glucagon-Like Peptide-1 Receptor Agonists in US Clinical Practice (STAY Study).

IntroductionReducing dosing frequency may lower treatment burden and improve persistence and adherence. This retrospective, observational study assessed persistence and adherence in patients with type 2 diabetes (T2D) initiating once-weekly or daily injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice.MethodsThe study used data from adults (≥ 18 years) with T2D who were included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre-index and ≥ 365 days post-index, were GLP-1 RA and insulin naïve at first claim (index date) for once-weekly or daily injectable GLP-1 RAs (follow-up: index date + 365 days), and were propensity score (PS) matched 1:1 by baseline characteristics. Persistence, defined as the stay time, was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Adherence was defined as a proportion of days covered of 0.8 or greater. To assess whether patients with more advanced disease would benefit from long-acting treatments, patients were matched to the baseline characteristics of basal insulin initiators using inverse probability of treatment weighting (IPTW).ResultsThe PS-matched cohorts (n = 784 each) had similar baseline characteristics. Once-weekly regimens were associated with significantly higher persistence than daily treatments (median stay time: 333 vs 269 days; hazard ratio 0.80 [95% confidence interval 0.71, 0.90]; p < 0.01) and with significantly higher adherence than daily regimens at 6 months and 12 months (p < 0.01 for both). Mean glycated haemoglobin reductions were greater with once-weekly than with daily treatment at 6 months (– 1.1% vs – 0.9%; p < 0.01) and 12 months (– 0.9% vs – 0.7%; p = not significant); adherent patients experienced greater reductions than those with poor adherence. Results were similar in the IPTW-matched analysis.ConclusionIn US clinical practice, once-weekly injectable treatments are associated with better persistence and adherence than daily regimens over 1 year. Once-weekly regimens may also benefit patients with more advanced T2D.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01189-6.

Perceptions of injectable therapies with cardiovascular benefit: an ACNAP survey of healthcare professionals to explore facilitators and barriers.

Injectable medicines are increasingly used to manage risk factors for cardiovascular (CV) events, such as dyslipidaemia and diabetes. These include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Little is known about perceptions of injectable therapies among CV healthcare professionals (HCPs). This study explores their views to identify relevant facilitators and barriers to the use of injectables with CV benefit. A 22-question survey was distributed internationally via online channels. In total, 192 anonymous responses were received (43.7% physicians, 32.6% nurses, 16.8% pharmacists, 6.8% others). Among respondents with experience of these medicines, 69.1% had used an injectable PCSK9 inhibitor and 67.0% had used an injectable GLP-1 receptor agonist. Commonly raised issues were resource problems (36.5%), lack of knowledge among colleagues (32.3%), paperwork (32.3%), and lack of patient knowledge (28.1%). Key barriers respondents felt made patients decline these treatments were fear of injection (56.6%), lack of awareness or education (26.4%), and administration issues (15.1%); potential reasons for discontinuation included side effects (46.4%), perceived lack of benefit (28.6%), and local reactions (21.4%). The main topics around injectables requiring further support included managing non-adherent patients (16.2%), troubleshooting with patients (16.2%), and educating colleagues about injectables (12.2%). Preferred educational methods to support HCPs were face-to-face training (43.5%) and online learning (26.1%); favoured formats were based on role playing and case studies. Healthcare professionals highlighted various potential barriers to initiation, continuation, and adherence with injectable therapies in CV medicine. Although some require healthcare system changes, many could be addressed through simple measures based primarily on enhanced training and support for patients and HCPs.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study

Aims To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). Methods Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. Results In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. Conclusions Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

83-LB: Adherence and Persistence in Patients with T2D Initiating Once-Weekly vs. Once-Daily Injectable GLP-1RA in U.S. Clinical Practice: STAY Study

Introduction: Reducing dosing frequency may reduce treatment burden and improve adherence and persistence. We assessed persistence and adherence in patients with T2D initiating once-weekly (OW) or once-daily (OD) injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in US clinical practice. Methods: Adults (≥ 18 years) with T2D included in the IBM MarketScan Explorys Claims-EMR Data Set for ≥ 180 days pre- and ≥ 365 days post-index, who were GLP-1 RA- and insulin-naïve at first claim for OW or OD injectable GLP-1 RA (index period: 1 Jul 2012-31 Jan 2019; follow-up: index date + 365 days), were propensity score matched 1:1 by age, sex, Charlson Comorbidity Index score, baseline HbA1c and weight (90 days pre-index), and use of sulfonylureas, metformin, DPP-4 inhibitors and SGLT-2 inhibitors (180 days pre-index). Persistence was defined as stay time (patients who had not discontinued [≥ 60 days not covered by medication] within 12 months were censored at 360 days) and assessed using Kaplan-Meier analysis and Cox proportional hazard models. Adherence was defined as proportion of days covered (PDC) ≥ 0.8. Results: The matched cohorts (n = 784 each) had similar characteristics. Compared with OD GLP-1 RAs, OW were associated with significantly higher persistence (median stay time, 333 days vs. 269 days; hazard ratio 0.80, p &amp;lt; 0.01) and better relative adherence at 6 months (+23%) and 12 months (+35%), irrespective of glycemic improvement and weight change. Mean HbA1c reduction was also greater for OW than for OD treatments at 6 months (-1.1% vs. -0.9%) and 12 months (-0.9% vs. -0.7%). Over 12 months, adherent patients experienced greater mean changes in HbA1c with both OW (-1.1%) and OD (-1.0%) regimens than patients with PDC &amp;lt; 0.8 (-0.6% each). Conclusions: Our results suggest that, in a real-world setting, OW injectable treatments are associated with better persistence and adherence than OD regimens, irrespective of glycemic or weight control. Disclosure A. Liebl: Advisory Panel; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MSD, Novo Nordisk, Roche, Speaker’s Bureau; Self; AstraZeneca, Bayer, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Dexcom, Inc., Eli Lilly and Company, Medtronic, MSD, Novo Nordisk, OmniaMed, Roche, Sanofi. R. Arora: Employee; Self; Novo Nordisk. M. Faurby: Employee; Self; Novo Nordisk A/S. J. Da rocha fernandes: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. W. H. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Inc., Consultant; Self; Abbott Diabetes, ADOCIA, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Novo Nordisk, Onduo LLC., Sanofi US. Funding Novo Nordisk A/S

The long-term cost-effectiveness of oral semaglutide in the Netherlands based on the PIONEER 2, 3 and 4 randomized controlled trials

AimsTo assess the long-term cost-effectiveness of novel glucagon-like peptide-1 (GLP-1) analog oral semaglutide versus sodium-glucose cotransporter-2 inhibitor empagliflozin, dipeptidyl peptidase-4 inhibitor sitagliptin and injectable GLP-1 analog liraglutide in the Netherlands, based on the results of the PIONEER clinical trials. MethodsOutcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Clinical data were derived from PIONEER 2, 3 and 4. Patients were assumed to receive initial treatments until glycated hemoglobin exceeded 7.5%, then treatment-intensified to basal insulin therapy. Costs were accounted from a societal perspective in 2019 euros (EUR). ResultsOral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.15, 0.22 and 0.09quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with combined costs EUR1,032 higher, EUR115 higher and EUR1,267 lower. Oral semaglutide was therefore associated with incremental cost-effectiveness ratios of EUR7,061 and EUR516 per QALY gained versus empagliflozin and sitagliptin, respectively. ConclusionsBased on long-term projections, oral semaglutide 14 mg was considered cost-effective versus empagliflozin 25 mg and sitagliptin 100 mg and dominant versus liraglutide 1.8 mg for the treatment of type 2 diabetes in the Netherlands.

Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis.

IntroductionThe relative efficacy and safety of once-daily oral semaglutide vs. injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in subjects with type 2 diabetes (T2D) inadequately controlled on basal insulin were assessed using network meta-analysis (NMA).MethodsA systematic literature review (SLR) was performed to identify randomised controlled trials of GLP-1 RAs in this population. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA1c), weight and blood pressure; HbA1c target levels (< 7.0% and ≤ 6.5%); composite endpoint; incidence of nausea, vomiting or diarrhoea. Comparators of interest were all licensed doses of dulaglutide, exenatide, liraglutide, lixisenatide and once-weekly injectable semaglutide.ResultsThe NMA included seven trials. Once-daily oral semaglutide 14 mg was associated with significantly greater HbA1c reductions vs. most comparators (treatment differences: − 0.42 to − 1.32%); differences vs. once-weekly injectable semaglutide (0.5 mg and 1 mg doses) were not statistically significant. Once-daily oral semaglutide 14 mg was associated with significantly greater weight reductions vs. exenatide 2 mg and lixisenatide 20 μg (− 2.21 and − 2.39 kg respectively); non-statistically significant weight reductions in favour of once-daily oral semaglutide 14 mg were observed vs. all other comparators except once-weekly injectable semaglutide 1 mg. Similar trends were observed for the proportion of subjects achieving HbA1c < 7.0% and ≤ 6.5% and the composite endpoint. Once-daily oral semaglutide 14 mg was associated with similar odds of experiencing nausea, vomiting or diarrhoea vs. all comparators.ConclusionOnce-daily oral semaglutide 14 mg, as an add-on to basal insulin, is an efficacious treatment for reducing HbA1c and weight and meeting glycaemic targets at 26 ± 4 weeks. Once-daily oral semaglutide 14 mg also offers the option of an oral treatment with similar or better efficacy and similar tolerability vs. most injectable GLP-1 RAs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01034-w.

Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: A meta-analysis.

Suboptimal medication adherence has been associated with increased resource utilisation and mortality among patients with type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly important in the treatment of T2D. However, medications in this class differ considerably in their dosing frequency, which may impact adherence. We sought to perform a meta-analysis to compare adherence to injectable GLP-1RAs dosed once weekly vs once daily in patients with T2D. Medline and Scopus were searched from 1/2005 to 7/2020 using keywords and MeSH terms pertaining to adherence and GLP-1RAs. Studies of adults with T2D were included if they compared adherence (as measured by proportion of days covered [PDC]) to injectable GLP-1RAs dosed once weekly vs once daily. A meta-analysis of non-overlapping studies was performed to evaluate the primary outcome of non-adherence, defined as the proportion of patients with a PDC<80. A total of 7 studies evaluating 75159 patients (range: 2886-30097) with T2D were included. The follow-up periods of included studies ranged from 6 to 12months. Injectable GLP-1RAs dosed once weekly were either dulaglutide, albiglutide or exenatide extended release; while liraglutide was the injectable once daily agent evaluated in all included studies. Upon meta-analysis, once weekly GLP-1RA dosing was associated with an 11% lower risk of non-adherence compared to once daily dosing (risk ratio=0.89; 95% confidence interval=0.83-0.95; I2 =89%). Once weekly dosing of injectable GLP-1RAs was associated with better adherence vs once daily dosing among patients with T2D. These findings coupled with the known detrimental consequences of non-adherence suggest that dosing frequency is an important factor to consider when selecting a GLP-1RA.

Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review.

Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], –0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

ObjectivesTo evaluate the efficacy and safety of the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) patients. Methods: Randomized controlled trials comparing oral semaglutide with placebo or other antihyperglycemic agents in T2DM patients were identified by searching PubMed, Embase, Cochrane Library and ClinicalTrials.gov. Risk ratios and mean differences with 95% confidence intervals were used to synthesize the results. Results: Ten relevant studies involving 8,536 patients were finally included. Compared with placebo, oral semaglutide significantly reduced hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, self-measured plasma glucose (SMPG), serious adverse events and all-cause death and significantly increased the number of participants who achieved HbA1c < 7.0%. Compared with active comparators, oral semaglutide significantly reduced the level of HbA1c, body weight, and SMPG and significantly increased the number of participants who achieved HbA1c < 7.0%. Compared with placebo or active comparators, oral semaglutide did not increase the incidence of adverse events, hypoglycemia (severe or blood glucose-confirmed symptomatic), myocardial infarction, heart failure requiring hospitalization, stroke or acute pancreatitis but did increase the incidence of nausea, diarrhea and vomiting. Conclusions: Oral semaglutide has favorable efficacy and safety in the treatment of T2DM patients. Oral semaglutide may be superior to liraglutide, dulaglutide, empagliflozin and sitagliptin for T2DM patients who have obesity or poor adherence to injectable GLP-1 RAs.

Type 2 diabetes in the US managed care setting: the burden of disease and rationale for an oral glucagon-like peptide-1 receptor agonist.

Diabetes affects an estimated 34 million US adults, with type 2 diabetes (T2D) accounting for 90% to 95% of cases. The downstream consequences of uncontrolled T2D are substantial, including an increased risk of microvascular complications (eg, renal impairment, retinopathy, and peripheral neuropathy), cardiovascular disease, impaired quality of life, and death. Overall, diabetes places a significant strain on the US health care system, with 7.8 million hospitalizations annually among patients with diabetes, and $237 billion in direct medical costs. Injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been available for T2D for over a decade, and are recommended, in particular, for patients with a compelling need to minimize hypoglycemia risk, curtail weight gain, or promote weight loss, and for patients with established cardiovascular disease. Despite being associated with high glucose-lowering efficacy, weight loss, and a low risk of hypoglycemia, injectable GLP-1RAs are relatively underutilized, and are associated with suboptimal adherence and persistence. These challenges may relate in part to the injectable route of administration, given that injection-related concerns have been linked with a failure to intensify T2D therapy in a timely manner (ie, therapeutic inertia), and are cited by patients as a barrier to initiating and persisting with injectable treatments. The approval of the first tablet formulation of a GLP-1RA for T2D, oral semaglutide, has the potential to address these challenges. In this context, we review the burden of T2D in the United States, the role of GLP-1RAs, the challenges of therapeutic inertia and poor adherence, and the rationale for an oral GLP-1RA, focusing on considerations for managed care.

Preference for Oral and Injectable GLP-1 RA Therapy Profiles in Japanese Patients with Type2 Diabetes: A Discrete Choice Experiment.

IntroductionGlucagon-like peptide 1 (GLP-1) receptor agonists (RAs) approved to date are administered by injection; therefore, patient perceptions of an oral GLP-1 RA are unknown. This discrete choice experiment explored preferences for (unbranded) oral and injectable GLP-1 RA profiles among Japanese patients with type 2 diabetes (T2D).MethodsAn online survey was designed using literature review and qualitative interview findings, and administered to Japanese patients with T2D and HbA1c ≥ 7.0% receiving oral antiglycaemic medication (with no experience of injectable antiglycaemic medication). Therapy profiles were created using Japanese head-to-head trial data for orally administered semaglutide (7 mg and 14 mg), injectable dulaglutide (0.75 mg), and injectable liraglutide (0.9 mg). Profiles were not labelled. Choice tasks tested preference between hypothetical profiles, preference between profiles with actual trial data, and willingness to initiate treatment. Relative importance of attributes was determined using conditional logit regression.ResultsA total of 500 respondents were analysed: mean age 61.2 years; 93.8% male; mean HbA1c 7.6%; 78.2% with HbA1c ≥ 7.0 to < 8%; 89% with HbA1c above personal target. Mean BMI was 25.4 kg/m2; 49% had obesity (≥ 25 kg/m2). The treatment attribute with greatest importance was mode and frequency of administration (49.1%), followed by nausea risk (30.8%), weight change (11.3%), and HbA1c change (8.8%). Oral semaglutide 7 and 14 mg-like profiles were both preferred: the 7 mg-like profile was preferred over dulaglutide (by 91.0% of respondents) and liraglutide (by 89.4%); the 14 mg-like profile was preferred over dulaglutide (by 88.2%) and liraglutide (by 94.4%). Willingness to initiate treatment was also higher for orally administered semaglutide-like profiles: 62.4% with 7 mg and 64.0% with 14 mg, versus 13.6% and 11.0% with injectable GLP-1 RA-like profiles. Subgroup results were generally consistent with the overall sample.ConclusionJapanese patients with T2D appear to prefer oral GLP-1 RA profiles over injectable GLP-1 RA profiles, and administration appears to be the most important factor in this decision. This highlights the unmet need for an effective and orally administered GLP-1 RA for the treatment of T2D in Japan.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-020-01561-1) contains supplementary material, which is available to authorized users.

&lt;p&gt;Real-World Adherence and Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists Therapy in Type 2 Diabetes Mellitus Patients in the United States&lt;/p&gt;

AimTo assess adherence and discontinuation of injectable glucagon-like peptide-1 receptor agonists (GLP-1 RA) at 12 and 24 months among adult type 2 diabetes mellitus (T2DM) patients in the United States initiating GLP-1 RA using the administrative claims-based database, Optum Clinformatics® Data Mart 7.1.MethodsA retrospective study was conducted from 01/2009 to 12/2017. Patients were required to be continuously enrolled for 12 months prior to their first GLP-1 RA prescription. Proportion of days covered (PDC) from prescription claims ≥0.80 defined adherence. Discontinuation was defined as a ≥90-day gap from the last date of GLP-1 RA supply to the first date of subsequent prescription claim.ResultsA total of 4791 T2DM patients had ≥1 and 3907 had ≥2 GLP-1 RA prescription claims. 50.9% and 47.4% of patients were adherent at 12 and 24 months, respectively. Adherence was significantly higher among patients on weekly vs daily doses (p<0.001). Median time to discontinuation was 13 months. The discontinuation rate was 47.7% and 70.1% at 12 and 24 months, respectively, with differences at 24 months for age and dosing frequency (p<0.001 for both).ConclusionOver half of T2DM patients initiating GLP-1 RA were non-adherent and the majority (70.1%) discontinued therapy by 24 months. Reasons for non-adherence and discontinuation merit further research.

Panniculitis at the Site of Injection: Infection or Foreign Body Reaction?

Abstract Introduction/Objective A 63 year old diabetic female presented to the dermatology clinic with painful abdominal nodules. The nodules seemed to wax and wane every 1–2 weeks and appeared in different locations on the abdomen. The lesions were subcutaneous, tender, firm, and mobile with no discoloration. The patient had diabetes treated with injectable exenatide but no other significant medical or travel history. Methods The differential diagnoses included mycobacterial infection, mechanical insult from injectable diabetes medication, erythema nodosum, erythema induratum, and lupus panniculitis. Ultrasound was indicative of panniculitis. A biopsy of the active lesion was performed. Results The biopsy showed septal and lobular panniculitis with mixed inflammation and multinucleated giant cells. Small, circular, non-polarizable pink amphorous material was associated with the infiltrate. The amphorous material was strongly acid fast. The patient had a negative quantiferon-TB test. Scanning electron microscopy with energy dispersive x-ray analysis showed that the material contained more oxygen and less carbon than surrounding tissue, but no abnormal elements were identified. Infrared spectroscopy of the foreign material most closely matched poly(L- lactide-co-glycolide). Conclusion The diagnosis of exenatide induced granulomatous panniculitis was made. The patient had recently started using this injectable glucagon-like peptide-1 receptor agonist, which has been associated with panniculitis. The injectable formulation is loaded onto microspheres composed of poly (DL-lactic-co-glycolic acid), which is closely related to poly(L-lactide-co-glycolide). This material has been shown to stain strongly acid fast. This case of granulomatous panniculitis due to injectable diabetic medication highlights an important potential pitfall that pathologists should be aware of, especially in cases where mycobacterial infection is in the differential.

Oral Semaglutide, A New Option in the Management of Type 2 Diabetes Mellitus: A Narrative Review.

According to current guidelines, glucagon-like peptide-1 (GLP-1) receptor agonists are the antidiabetic agent of choice in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) and are also the preferable antidiabetic agent in patients with T2DM without CVD but with indicators of high cardiovascular risk. A limitation in the use of GLP-1 receptor agonists is that they are delivered by subcutaneous injections. In this context, the development of an orally administered formulation of semaglutide offers an additional option in the management of patients with T2DM. In the present review, we discuss the findings of the main trials that evaluated the safety and efficacy of oral semaglutide. Oral semaglutide appears to be more effective in reducing HbA1c levels and body weight than other antidiabetic agents and similarly effective to other GLP-1 receptor agonists. The safety profile of oral semaglutide is also comparable with other members of its class. Even though oral semaglutide did not reduce the incidence of the composite primary endpoint in a randomized controlled trial, a reduction in cardiovascular and all-cause mortality was observed. Therefore, oral semaglutide appears to represent a useful tool in the management of patients with TD2M, particularly those with established CVD or high cardiovascular risk and unwilling to receive injectable GLP-1 receptor agonists.

Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial).

Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Effect of dulaglutide on liver fat (D-LIFT) was a 24week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes. Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of -3.5% (95% CI -6.6, -0.4; p = 0.025) and relative change of -26.4% (-44.2, -8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference -13.1U/l [95% CI -24.4, -1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (-9.3U/l [-19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (-13.1U/l [-24.4, 2.5]; p = 0.10). Absolute changes in PFC (-1.4% [-3.2, 0.3]; p = 0.106) and LSM (-1.31kPa [-2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events. When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes. ClinicalTrials.gov NCT03590626 FUNDING: The current study was supported by an investigator-initiated study grant from Medanta-The Medicity's departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India. Graphical abstract.

Optimizing Therapeutic Outcomes With Oral Semaglutide: A Patient-Centered Approach.

In September 2019, the U.S. Food and Drug Administration approved oral semaglutide as the first orally administered glucagon-like peptide 1 (GLP-1) receptor agonist for treating people with type 2 diabetes. Although injectable GLP-1 receptor agonists are well-established treatment options for people with type 2 diabetes, clinical experience with an oral formulation in this class is limited. This article provides practical guidance for diabetes care and education specialists on how to effectively counsel patients initiating therapy with oral semaglutide on appropriate administration of the treatment and its possible effects on glycemic control, body weight, and quality of life. Strategies for mitigating potential side effects typical of the GLP-1 receptor agonist class, namely nausea, vomiting, and diarrhea, are also provided. Involving patients in treatment decisions and educating them about available and prescribed medications are key strategies for encouraging treatment adherence and ensuring optimal therapeutic outcomes.

Nasal absorption enhancement of protein drugs independent to their chemical properties in the presence of hyaluronic acid modified with tetraglycine-L-octaarginine

Our previous mouse studies demonstrated that mean bioavailability of exendin-4, which is an injectable glucagon-like peptide-1 (GLP-1) analogue whose molecular weight (Mw) and isoelectric point (pI) are ca. 4.2 kDa and 4.5, respectively, administered nasally with poly(N-vinylacetamide-co-acrylic acid) (PNVA-co-AA) bearing D-octaarginine, which is a typical cell-penetrating peptide, was 20% relative to subcutaneous administration even though it was less than 1% when exendin-4 alone was given nasally. The studies also revealed that the absorption-enhancing ability of D-octaarginine-linked PNVA-co-AA for exendin-4 was statistically equivalent to that of sodium salcaprozate (SNAC), which is an absorption enhancer formulated in tablets of semaglutide approved recently as an orally available GLP-1 analogue. From a perspective of clinical application of our technology, we have separately developed hyaluronic acid modified with L-octaarginine via a tetraglycine spacer which would be degraded in biological conditions. The present study revealed that tetraglycine-L-octaarginine-linked hyaluronic acid enhanced nasal absorption of exendin-4 in mice, as did D-octaarginine-linked PNVA-co-AA. There was no significant difference in absorption-enhancing abilities between the hyaluronic acid derivative and SNAC when octreotide (Mw: ca. 1.0 kDa, pI: 8.3) and lixisenatide (Mw: ca. 4.9 kDa, pI: 9.5) were used as a model protein drug. On the other hand, SNAC did not significantly enhance nasal absorption of somatropin (Mw: ca. 22.1 kDa, pI: 5.3) when compared with absorption enhancer-free conditions. Substitution of SNAC with tetraglycine-L-octaarginine-linked hyaluronic acid resulted in a 5-fold increase in absolute bioavailability of somatropin with statistical significance. It appeared that pI hardly ever influenced absorption-enhancing abilities of both enhancers. Results indicated that our polysaccharide derivative would be a promising absorption enhancer which delivers biologics applied on the nasal mucosa into systemic circulation and was of greater advantage than SNAC for enhancing nasal absorption of protein drugs with a larger Mw.

Safety of injectable semaglutide for type 2 diabetes

ABSTRACT Introduction Semaglutide is the most recently approved injectable glucagon-like peptide-1 receptor agonist (GLP-1RA) for people with type 2 diabetes (T2DM). It is one of the three currently marketed GLP-1RAs that can be administered once weekly. Areas covered This review focusses on the safety of injectable semaglutide. Semaglutide has been assessed in the SUSTAIN phase 3 clinical trial programme, which included patients across the disease spectrum, i.e. treatment-naïve to those receiving insulin. The authors have looked at all published literature on safety considerations of once weekly GLP-1RA with particular reference to semaglutide. Expert opinion Semaglutide is the most powerful injectable GLP-1RA. The cardiovascular (CV) outcome trial (SUSTAIN 6) showed CV superiority and its adverse event profile is as expected for the GLP-1RA class with predominantly gastrointestinal side-effects. Concerns about the thyroid and pancreatic safety have not been substantiated. There is no indication of renal or liver harm for semaglutide. Data consistent with reno-protection and benefit in liver disease is presented. There is a modest signal for increased gall bladder adverse events. An increase in diabetic retinopathy (DR) events in the SUSTAIN 6 trial is the most concerning safety signal. Caution regarding DR is needed when initiating semaglutide and recommendations are suggested.