Glucagon-like Peptide-1 Receptor Agonist Therapy Research Articles

S1349 Glucagon-Like Peptide-1 Receptor Agonist and Pioglitazone Therapy Have Superior Mortality and Liver Outcomes for Patients With Type 2 Diabetes and a Diagnosis or at Risk for Undiagnosed Non-alcoholic Fatty Liver Disease

S1349 Glucagon-Like Peptide-1 Receptor Agonist and Pioglitazone Therapy Have Superior Mortality and Liver Outcomes for Patients With Type 2 Diabetes and a Diagnosis or at Risk for Undiagnosed Non-alcoholic Fatty Liver Disease

Efficacy and safety of glucagon-like peptide-1 receptor agonists therapy initiation in patients with type 2 diabetes hospitalized with coronavirus infection

BACKGROUND. The search for new effective methods of treatment and prevention of COVID-19 in patients with type 2 diabetes mellitus (T2DM) remains an urgent task for the healthcare system.AIM. To evaluate the efficacy and safety of initiating of glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy in T2DM patients hospitalized with COVID-19.MATERIALS AND METHODS. The inclusion criteria were history of T2DM, BMI> 27 kg/m2, confirmed diagnosis of COVID-19. The intervention group of 53 patients started dulaglutide therapy (1,5 mg once weekly) during the first 24 hours of admission, the control group consisted of 50 patients, who proceeded with glucose-lowering therapy. We evaluated the effect of therapy on carbohydrate metabolism, laboratory and clinical parameters, the outcome of COVID-19 and the safety of therapy (hypoglycemic events, side effects).RESULTS. There were no differences found in the degree of decrease in the level of glycemia in the compared groups: fasting plasma glucose (FPG) on day 7 of hospitalization– 8,2 [6,0;9,8] mmol/L vs 8,1 [6,5;9,8] mmol/L (p=0,935), mean daily glycemia (MDG) — 9,7 [8,3;11,8] mmol/L vs 11,1 [8,7;12,8] mmol/L (p=0,182). Therapy of dulaglutide had a positive effect on inflammatory markers: CRP (15,8 vs 24,4 mg/l, p=0,035), LDH (261,6 vs 326,1 U/l, p=0,016) and the level of lymphocytes (1,2 vs 0,9 x 10*9/L, p=0,049) and on clinical parameters: saturation, the need for oxygen therapy and the risk of severe course according to the NEWS2 scale. The death rate in the group receiving GLP-1RA is 3,5 times lower compared to the control group (5,7% vs 20,0%, p=0,038). The initiation of dulaglutide therapy in patients with T2DM hospitalized with COVID-19 reduced the chance of death and transfer to mechanical ventilation by 4,2 times compared to the control group (OR = 0,24, 95% CI: 0,062–0,931). GLP-1RA therapy in patients with COVID-19 and T2DM is safe in terms of hypoglycemic events and side effects.CONCLUSIONS. The initiation of GLP-1RA therapy leads to a decrease in FPG and MDG, comparable with the control group. The start of GLP-1RA therapy in hospitalized patients with COVID-19 and T2DM reduces the chance of death, favorably affecting on laboratory and clinical parameters.

Do GLP-1 Analogs Have a Place in the Treatment of PCOS? New Insights and Promising Therapies.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy in women of reproductive age. This condition is characterized by hyperandrogenism and either oligo- or anovulation. PCOS patients often present comorbidities such as obesity, insulin resistance, impaired glucose metabolism, dyslipidemia, hypertension, metabolic syndrome, and an increased risk of diabetes. Given the profound implications of metabolic impairment in PCOS, the accurate diagnosis and management of these facets are imperative. The first-line approach to treatment involves lifestyle modifications, including dietary adjustments and exercise aimed at achieving weight loss, a strategy consistently emphasized across the literature. Supplementation with probiotics, vitamin D, and L-carnitine have also provided additional benefits to patients. In select cases, pharmacological interventions are needed for optimal therapeutic results. The most common medications used in PCOS include metformin, thiazolidinediones, inositols, and two classes of antidiabetic agents: dipeptidyl peptidase-IV (DPP-IV) inhibitors, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a new addition to the therapeutic arsenal for the metabolic management of PCOS. GLP-1 receptor agonists cause insulin release in a glucose-dependent manner, yielding clinical benefits such as heightened satiety, reduced appetite, and appetite regulation. GLP-1RAs have demonstrated efficacy in reducing glycated hemoglobin levels and promoting weight loss while ameliorating hyperlipidemia. Prior to initiating GLP-1RA therapy, patients should undergo screening for contraindications, including history of pancreatitis, diabetic retinopathy, or thyroid cancer. The effects of treatment should be monitored using laboratory testing and body weight measurements. Effective communication between clinician and patient should be maintained with regular check-in for a period of 6 to 12 months.

Comparison of the efficacy and safety of hypoglycemic treatments in patients with non-alcoholic fatty liver disease and type-2 diabetes: a systematic review and Bayesian network analysis.

The association between non-alcoholic fatty liver disease (NAFLD) and metabolic disorders, especially type-2 diabetes (T2DM), has been proven to be bidirectional. Hypoglycemic agents may be promising treatments for those disorders. However, there is currently no approved hypoglycemic therapy for NAFLD. In this review, we aimed to compare the efficacy and safety of twelve different hypoglycemic treatments in patients with NAFLD and T2DM. We systematically screened randomized controlled trials (RCTs) published from March 2013 to March 2023 by searching PubMed, Embase, Medline, and Web of Science without any language restriction. We registered this project on the PROSPERO website: https://www.crd.york.ac.uk/PROSPERO/ (ID: CRD42023429701). All subsequent analyses were performed under the registered protocol. The mean difference (MD) and 95% confidence interval (95% CI) were adapted to evaluate the effect size of the treatment. The surface under the cumulative sorting curve (SUCRA) was used to rank the efficacy of the included treatments. We included 19 trials involving 1212 patients in total. Insulin plus glucagon-like peptide-1 receptor agonist (GLP1RA) combination therapy was probably the most effective treatment for reducing weight and body mass index (BMI) (SUCRA: 0.93 and 1.00). Thiazolidinediones (TZD) were probably the most effective treatment for reducing glycosylatedhemoglobin (HbA1c) and γ-glutamyltranspeptidase (γ-GGT) levels (SUCRA: 0.78 and 0.97). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) had the highest probability of presenting good therapeutic efficacy in reducing triglyceride (TG) levels (SUCRA: 0.72). The most common adverse reactions were gastrointestinal disorders, mainly after the administration of GLP1RA, and mild hypoglycemia, which was closely related to the use of insulin. GLP1RA plus insulin combination therapy, GLP1RA, SGLT2i, and TZD may be the most effective therapeutic methods for patients with NAFLD and T2DM.

SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study

Aims/hypothesisInsulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes.MethodsWe performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy.ResultsWe identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA1c (−2.6 mmol/mol [−0.2%] with SGLT2i and −5.4 mmol/mol [−0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m2 vs −7.2 ml/min per 1.73 m2, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort.Conclusions/interpretationBoth SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes.Graphical

A beneficial role of GLP-1 receptor agonist therapy in ABCC8-MODY (MODY 12)

Maturity-onset diabetes of the young (MODY) is an inherited form of diabetes resulting from a mutation in a single gene. ABCC8-MODY is caused by mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), a regulatory component of the ATP-sensitive potassium (KATP) channel found in beta cells. In ABCC8-MODY, mutations in the ABCC8 gene interfere with insulin secretion in response to glucose. Recent evidence suggests that therapy with GLP-1 receptor agonists (GLP-1 RAs) may be beneficial in ABCC8-MODY. This report presents a successful treatment of a 49-year-old woman diagnosed with ABCC8-MODY using the GLP-1 RA semaglutide. The patient, who had been previously receiving insulin therapy, experienced significant improvements in glycemic control and weight loss after transitioning to semaglutide. GLP-1 RAs potentially enhance insulin secretion in ABCC8-MODY by activating multiple signaling pathways involved in insulin secretion. The report highlights the potential of GLP-1 RA therapy as an alternative to sulfonylureas and insulin for individuals with ABCC8-MODY. GLP-1 RAs have previously demonstrated benefits in other forms of MODY. Understanding the molecular mechanisms through which GLP-1 RAs promote insulin secretion, including their effects on KATP channels and activation of PKA and Epac signaling, offers valuable insights into their therapeutic effects.

Characteristics predicting the efficacy of SGLT-2 inhibitors versus GLP-1 receptor agonists on major adverse cardiovascular events in type 2 diabetes mellitus: a meta-analysis study

BackgroundRecent large clinical trials have demonstrated cardiovascular benefits of similar overall magnitude for sodium–glucose cotransporter-2 inhibitor (SGLT-2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in subjects with type 2 diabetes. We sought to identify subgroups based on baseline characteristics with a differential response to either SGLT-2i or GLP-1RA.MethodsPubMed, Cochrane CENTRAL, and EMBASE were searched from 2008 to 2022 for SGLT-2i or GLP-1RA randomized trials that reported 3-point major adverse cardiovascular events (3P-MACE). Baseline clinical and biochemical characteristics included age, sex, body mass index (BMI), HbA1c, estimated glomerular filtration rate (eGFR), albuminuria, preexisting cardiovascular disease (CVD), and heart failure (HF). Absolute and relative risk reductions (ARR and RRR) regarding incidence rates for 3P-MACE with a 95% confidence interval were calculated. The association of average baseline characteristics in each study with the ARR and RRR for 3P-MACE was investigated by meta-regression analyses (random-effects model, assuming inter-study heterogeneity). Meta-analysis was also conducted to investigate whether the efficacy of SGLT-2i or GLP-1RA on 3P-MACE reduction could differ according to the patient’s characteristics (e.g., HbA1c above/below cutoff).ResultsAfter a critical assessment of 1,172 articles, 13 cardiovascular outcome trials with a total of 111,565 participants were selected. In meta-regression analysis, the more patients with reduced eGFR in the studies, the greater ARR by SGLT-2i or GLP-1RA therapy. Similarly, in the meta-analysis, SGLT-2i therapy tended to be more effective in reducing 3P-MACE in people with eGFR < 60 ml/min/1.73 m2 than in those with normal renal function (ARR − 0.90 [–1.44 to − 0.37] vs. − 0.17 [–0.34 to − 0.01] events/100 person-years). Furthermore, people with albuminuria tended to respond better to SGLT-2i therapy than those with normoalbuminuria. However, this was not the case for the GLP-1RA treatment. Other factors including age, sex, BMI, HbA1c, and preexisting CVD or HF did not affect the efficacy of either SGLT-2i or GLP-1RA treatment on the ARR or RRR of 3P-MACE.ConclusionsBecause decreased eGFR [significant] and albuminuria [trend] were found to predict a better efficacy for SGLT-2i in 3P-MACE reduction, this class of drug should be preferred in such patients. However, GLP-1RA may be considered for patients with normal eGFR because it showed better efficacy than SGLT-2i in this subgroup [trend].

84-LB: Intensification of Glucagon-Like Peptide-1 Receptor Agonists Therapy with Glargine 300 U/mL or IDegLira—The RESTORE-G Real-World Study

Combined use of basal insulin (BI) and glucagon-like peptide 1 receptor agonist (GLP1-RA) deserves consideration for the synergistic effects on glucose profile. Nevertheless, it is unclear if the addition of BI to the ongoing GLP1-RA therapy in free or fixed combination is associated with different outcomes. Aim of this RESTORE-G sub-study was to perform a propensity-score adjusted comparative effectiveness analysis of the two most innovative BIs for intensifying GLP1-RA therapy (±oral agents), i.e. Glargine 300 U/mL in free combination (Gla-300) vs. the fixed ratio combination of insulin degludec + liraglutide (IDegLira). Table shows sample sizes, patients characteristics and effectiveness results. Compared to IDegLira, Gla-300 group had older age, worse metabolic control, and higher starting BI doses. After 6 months, statistically significant larger FBG reduction and BI dose increase were found in the free vs. fixed combination group. Trends of larger HbA1c and weight reductions with the free combination were also found, without reaching the statistical significance. In conclusion, higher benefits on FBG control in free vs. fixed combination has been found in people uncontrolled on GLP-1 RA, likely due to a better titration of the components. However, inertia in insulin initiation was documented in both groups. Disclosure R. Candido: None. A. Nicolucci: Board Member; AstraZeneca, Research Support; Novo Nordisk, Sanofi, Sobi, Shionogi &amp; Co., Ltd., AlfaSigma, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. M. Rossi: Research Support; Sanofi, Novo Nordisk, Shionogi &amp; Co., Ltd., AlfaSigma. M. Larosa: None. R. Napoli: Advisory Panel; Sanofi, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk, AstraZeneca, Speaker's Bureau; Sanofi, Eli Lilly and Company, Novo Nordisk, AstraZeneca, MSD Life Science Foundation. Restore-g study group: n/a. Funding Sanofi

779-P: Intensification of Glucagon-Like Peptide-1 Receptor Agonists Therapy with First and Second Generation Basal Insulins—The RESTORE-G Real-World Study

ADA guidelines suggest that in patients needing insulin treatment, combination therapy with a glucagon-like peptide 1 receptor agonist (GLP1-RA) is recommended for greater efficacy, durability of treatment effect, and weight and hypoglycemia benefit. However, when treatment with GLP1-RA needs to be intensified, switch to insulin approach is still very common. It is also known that second generation basal insulins (2BI) provide similar or improved efficacy with a better safety profile compared to first generation basal insulins (1BI). Aim of this RESTORE-G sub-study was to perform a propensity-score adjusted comparative effectiveness analysis of adding-on/switching to 2BI vs. 1BI in patients on GLP1-RA therapy (±oral hypoglycemic agents) needing intensification. Table shows sample sizes, patients characteristics and effectiveness results. Data shows that 2BI vs. 1BI was associated with significantly larger improvements in HbA1c and FBG both in add-on and switch approaches. In the switch approach, 2BI produced lower weight gain versus 1BI. Switching vs. adding on was associated with a more frequent use of short acting insulin. Both 1BI and 2BI were poorly titrated. Disclosure R.Napoli: Advisory Panel; Sanofi, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk, AstraZeneca, Speaker's Bureau; Sanofi, Eli Lilly and Company, Novo Nordisk, AstraZeneca, MSD Life Science Foundation. M.Larosa: None. A.Nicolucci: Board Member; AstraZeneca, Research Support; Novo Nordisk, Sanofi, Sobi, Shionogi &amp; Co., Ltd., AlfaSigma, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. M.Rossi: Research Support; Sanofi, Novo Nordisk, Shionogi &amp; Co., Ltd., AlfaSigma. R.Candido: None. Restore-g study group: n/a. Funding Sanofi

Evaluation of effects of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors on estimated glomerular filtration rate, albuminuria and weight in diabetic kidney disease: A prospective cohort study

Introduction: Albuminuria and baseline estimated glomerular filtration rate (eGFR) are the main predictors for progression of diabetic kidney disease (DKD). Objectives: The objectives of the study were to assess the effects of GLP1-RA (glucagon-like peptide-1 receptor agonists) and SGLT2i inhibitors therapy on estimated GFR, albuminuria, and weight in patients with DKD stage 3 and 4. Patients and Methods: This was a prospective cohort study of patients with stage 3 and 4 DKD over 6 months at Basra teaching hospital from November 1, 2020, to May 1, 2020. Baseline weight, UACR (urine albumin creatinine ratio), and eGFR were measured, and 6-months values were assessed between and within the group. Results: The baseline characteristics for the GLP-1 RA (GLP-1 receptor agonists) versus SGLT2i (sodium-glucose co-transporter-2 inhibitors) groups were mean ages 65 years versus 62.5 years, male (54.5% versus 50%), median weight (75 versus 80 kg), median eGFR (23.5 versus 39 ml/min/1.73 m2 ) and median UACR (925 mg/g versus 327 mg/g). In the GLP-1 RA group, after 6-months of therapy, there was 32% increase in eGFR (P&lt;0.001), 29% decrease in UACR (P&lt;0.001) and 4.5% decrease in weight while in the SGLT2i group, there was 4.5% decrease in eGFR (P=0.345), 34% decrease in UACR (P&lt;0.001) and 2.8% decrease in weight (P=0.005). With cox-regression analysis, the HR for eGFR decline with SGLT2i therapy was 3.25 (95% CI: 1.1-9.97; P=0.039). Conclusion: GLP-1 RA, compared to SGLT2i therapy, caused an increase in eGFR in stages 3 and 4 CKD and caused more weight reduction but slightly less albuminuria reduction.

Glycemic control and its associated factors in hypertensive patients with type 2 diabetes.

Inadequate glycemic control among patients with type 2 diabetes is growing worldwide. Earlier research studies investigated the predictors of poor glycemic control among patients with diabetes, but not among hypertensive patients who have type 2 diabetes as a comorbid disease. The aim of this study was to explore the factors associated with poor glycemic control in patients with type 2 diabetes and hypertension. In the present retrospective study, the medical records of two major hospitals were used to collect sociodemographic, biomedical, disease and medication-related information about patients with hypertension and type 2 diabetes. Binary regression analysis was conducted to find the predictors of the study outcome. The data from 522 patients were collected. High physical activity (OR=2.232; 95% CI: 1.368-3.640; p<0.01), receiving insulin (OR=5.094; 95% CI: 3.213-8.076; p <0.01) or GLP1 receptor agonist (OR=2.057; 95% CI: 1.309-3.231; p<0.01) increased the odds of having controlled blood glucose. Increased age (OR=1.041; 95% CI: 1.013-1.070; p<0.01), elevated high-density lipoprotein (HDL) levels (OR=3.727; 95% CI: 1.959-7.092; p<0.01), and lower triglycerides (TGs) levels (OR=0.918; 95% CI: 0.874-0.965; p<0.01) were also associated with improved glycemic control among the study participants. Most of the current study participants showed uncontrolled type 2 diabetes. Low physical activity, not receiving insulin or GLP1 receptor agonist, younger age, low HDL and high TG levels were independently associated with poor glycemic control. Future interventions should place a strong emphasis on the value of consistent physical activity and a stable lipid profile in enhancing glycemic control, particularly in younger patients and those who are not receiving insulin or GLP1 receptor agonist therapy.

Association of Prescription Co-payment With Adherence to Glucagon-Like Peptide-1 Receptor Agonist and Sodium-Glucose Cotransporter-2 Inhibitor Therapies in Patients With Heart Failure and Diabetes

Type 2 diabetes (T2D) and heart failure (HF) prevalence are rising in the US. Although glucagon-like peptide-1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve outcomes for these conditions, high out-of-pocket costs may be associated with reduced medication adherence. To compare 1-year adherence to GLP1-RA and SGLT2i therapies by prescription co-payment level in individuals with T2D and/or HF. This retrospective cohort study used deidentified data from Optum Insight's Clinformatics Data Mart Database of enrollees with commercial and Medicare health insurance plans. Individuals aged 18 years or older with T2D and/or HF who had a prescription claim for a GLP1-RA or SLGT2i from January 1, 2014, to September 30, 2020, were included. Prescription co-payment, categorized as low (<$10), medium ($10 to<$50), and high (≥$50). The primary outcome was medication adherence, defined as a proportion of days covered (PDC) of 80% or greater at 1 year. Logistic regression models were used to examine the association between co-payment and adherence, adjusting for patient demographics, medical comorbidities, and socioeconomic factors. A total of 94 610 individuals (mean [SD] age, 61.8 [11.4] years; 51 226 [54.1%] male) were prescribed GLP1-RA or SGLT2i therapy. Overall, 39 149 individuals had a claim for a GLP1-RA, of whom 25 557 (65.3%) had a PDC of 80% or greater at 1 year. In fully adjusted models, individuals with a medium (adjusted odds ratio [AOR], 0.62; 95% CI, 0.58-0.67) or high (AOR, 0.47; 95% CI, 0.44-0.51) co-payment were less likely to have a PDC of 80% or greater with a GLP1-RA compared with those with a low co-payment. Overall, 51 072 individuals had a claim for an SGLT2i, of whom 37 339 (73.1%) had a PDC of 80% or greater at 1 year. Individuals with a medium (AOR, 0.67; 95% CI, 0.63-0.72) or high (AOR, 0.68; 95% CI, 0.63-0.72) co-payment were less likely to have a PDC of 80% or greater with an SGLT2i compared with those with a low co-payment. In this cohort study of individuals with T2D and/or HF, 1-year adherence to GLP1-RA or SGLT2i therapies was highest among individuals with a low co-payment. Improving adherence to guideline-based therapies may require interventions that reduce out-of-pocket prescription costs.

Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease—Current Background, Hopes, and Perspectives

Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease worldwide, reaching one of the highest prevalences in patients with type 2 diabetes mellitus (T2DM). For now, no specific pharmacologic therapies are approved to prevent or treat NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are currently evaluated as potential candidates for NAFLD treatment in patients with T2DM. Some representatives of this class of antihyperglycemic agents emerged as potentially beneficial in patients with NAFLD after several research studies suggested they reduce hepatic steatosis, ameliorate lesions of nonalcoholic steatohepatitis (NASH), or delay the progression of fibrosis in this population. The aim of this review is to summarize the body of evidence supporting the effectiveness of GLP-1RA therapy in the management of T2DM complicated with NAFLD, describing the studies that evaluated the effects of these glucose-lowering agents in fatty liver disease and fibrosis, their possible mechanistic justification, current evidence-based recommendations, and the next steps to be developed in the field of pharmacological innovation.

An Investigation on the Efficacy of Glucagon-Like Peptide 1 Receptor Agonists Drugs in Reducing Urine Albumin-to-Creatinine Ratio in Patients With Type 2 Diabetes: A Potential Treatment for Diabetic Nephropathy.

As diabetes mellitus becomes increasingly prevalent globally, so does diabetic nephropathy, a complication leading to one of the world's leading causes of end-stage renal disease (ESRD). Current research has linked an increase in the urine albumin-to-creatinine ratio (UACR), a marker for kidney damage, to a greater risk of adverse renal outcomes and ESRD in patients with diabetes. Of the diabetes medications studied and implemented in clinical settings, glucagon-like peptide-1 receptor agonist (GLP1-RA) drugs have been shown to not only help control HbA1c in diabetes but have also demonstrated numerous cardiovascular, hepatic, and renal benefits. The objective of our study was to assess the efficacy of GLP1-RA drugs in reducing UACR in patients with type 2 diabetes mellitus (T2 DM) to determine if GLP1-RAs could be used to provide renoprotection in diabetic nephropathy in addition to their glucose-lowering effects. Upon a comprehensive review of the literature, we conducted a statistical analysis to determine the efficacy of GLP1-RA monotherapy and combination therapy in reducing UACR in comparison to placebo and insulin glargine. Of the studies analyzed, GLP1-RAs exhibited a statistically significant effect in reducing UACR in comparison to a placebo but not in comparison to insulin glargine. GLP1-RA combination therapy (GLP1-RA used with either insulin glargine, metformin, or dapagliflozin) did not exhibit statistically significant UACR reductions in comparison with insulin glargine. However, GLP1-RA combination therapy showed a trend suggestive of being more effective than insulin glargine in reducing UACR, but due to the limited literature studying this treatment method, further studies in a more focused group of patients with diabetic nephropathy may produce stronger and more definitive results. GLP1-RA monotherapy or combination therapy has been determined to be an effective method for reducing UACR and decreasing the incidence of adverse renal outcomes associated with diabetic kidney disease. GLP1-RA therapy could serve as an alternative treatment in diabetic nephropathy to insulin glargine, which carries a higher risk of hypoglycemia and unintentional weight gain while potentially being less cost-effective.

Value of GLP-1 receptor agonists versus long-acting insulins for type 2 diabetes patients with and without established cardiovascular or chronic kidney diseases: A model-based cost-effectiveness analysis using real-world data

AimsTo evaluate the cost-effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) versus long-acting insulins (LAIs) in patients with type 2 diabetes (T2D) using real-world data. MethodsA Markov model was utilized to estimate healthcare costs (US$) and quality-adjusted life-years (QALYs) of receiving treatments over 10 years from the healthcare sector perspective. Model inputs were derived from the analyses of Taiwan’s National Health Insurance Research Database or published literature on Taiwanese T2D populations. Base-case analysis was performed for the overall study cohort and subgroup analyses were stratified by the presence or absence of established cardiovascular diseases (CVDs) or chronic kidney diseases (CKDs). ResultsOverall, using GLP-1RAs versus LAIs cost $6,053 per QALY gained. Results were robust across sensitivity and scenario analyses. Among patients with established CVDs and CKDs, GLP-1RA versus LAI therapy saved $673 (cost-saving) and cost $1,675 per QALY gained, respectively. Among patients without established CVDs and CKDs, GLP-1RA versus LAI therapy cost $9,093 and $7,659 per QALY gained, respectively. ConclusionsUsing GLP-1RAs versus LAIs for T2D patients represented good economic value in real-world practice. Pronounced economic benefits of GLP-1RA therapy among those with prior CVDs or CKDs support rational treatment decisions and optimal healthcare resource allocation for these patients.

The Possible Effect of the Long-Term Use of Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) on Hba1c and Lipid Profile in Type 2 Diabetes Mellitus: A Retrospective Study in KAUH, Jeddah, Saudi Arabia.

(1) Background: Type 2 diabetes (T2DM) is a chronic metabolic disease with serious health complications. T2DM is associated with many chronic illnesses, including kidney failure, cardiovascular diseases (CVD), vision loss, and other related diseases. Obesity is one of the major factors associated with insulin resistance and dyslipidemia. Recently, the development of GLP-1 Receptor agonist (GLP-1RA) showed great therapeutic potential for T2DM. Aim: To retrospectively investigate the association of the long-term use of GLP-1RA therapy in T2DM patients with HbA1c levels and dyslipidemia. (2) Methods: Retrospective data collection and analysis of demographic, clinical records, and biochemical parameters were carried out for 72 T2DM taking GLP-1RA treatments for six months. (3) Results: A total of 72 T2DM patients with a mean age = 55 (28 male and 44 female) were divided into two groups. Group 1 received statins (n = 63), and group 2 did not receive statins (n = 9). The GLP-1RA effect on BMI was significantly decreased in group 1 (p < 0.01). A significant effect was observed for HbA1c in both groups for six months of treatment duration (p < 0.05). The AST levels significantly decreased in group 2 from 25.2 to 19.4 U\L (p = 0.011). (4) Conclusions: GLP-1RA treatments were associated with weight reduction and improved glycemic control for T2DM patients. Moreover, it is suggested that it has anti-inflammatory and hepatoprotective effects. However, no direct association was found with the lipid profile in all groups of T2DM.

The GLP-1 receptor agonist exenatide reduces serum TSH by its effect on body weight in people with type 2 diabetes.

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in patients with type 2 diabetes and obesity leads to a significant reduction in serum thyrotropin (TSH) levels but it is unclear whether this is related to weight loss and improvement in sensitivity to thyroid hormones (TH). We prospectively analysed clinical and biochemical data in patients with type 2 diabetes and obesity who were commenced on the GLP-1 RA exenatide and followed them for 12 months. We assessed the relationship between changes in body weight and serum TSH and resistance to TH indices. In 112 patients (mean age: 53.5 years, 43.8% female, mean body mass index: 39.8 kg/m2 ), 12 months of exenatide treatment was associated with a mean (95% CI) percent body weight loss of 6.5% (5.0%-8.1%) and change in serum TSH of -0.25 mU/L (-0.43 to -0.06). There was a significant negative and nonlinear relationship between change in serum TSH and percent body weight loss: -0.25 mU/L with 5%, -0.4 mU/L with 10% and -0.5 mU/L with 15%, respectively, whereas a rise in serum TSH of 0.5 mU/L was associated with 5% weight gain. There were no changes observed in serum FT4 levels with weight loss but a significant reduction in resistance to TH indices was noted. Exenatide therapy reduces serum TSH levels and improves central sensitivity to TH action over 12 months via its effect on weight loss. The effectiveness of weight loss strategies, rather than TH replacement, should be investigated in individuals with obesity and mildly raised serum TSH levels.

Vitreous hemorrhage during GLP-1 receptor agonist treatment

BackgroundThe purpose of this case report is to describe a case of vitreous hemorrhage in a patient with a history of diabetic retinopathy and receiving dulaglutide for the management of type 2 diabetes mellitus (T2DM). Case summaryA 64-year-old African American male with a past medical history of T2DM and severe diabetic retinopathy for 4 years was restarted on dulaglutide 1.5 mg weekly after being off therapy for 3 months. Baseline laboratory test results included hemoglobin A1c (HbA1c) of 8.8% and random blood glucose (BG) of 280 mg/dL. In addition, the patient had an average fasting BG of 150 mg/dL. In absence of intolerance, the dulaglutide dose was gradually maximized to 4.5 mg weekly and HbA1c decreased to 7.3% and random BG to 121 mg/dL at week 12 since reinitiation. At week 17 of therapy, the patient presented to the emergency department with a 1-day history of vision loss in the left eye and was diagnosed as having vitreous hemorrhage. The etiology for vitreous hemorrhage is unclear and may be a spontaneous episode. In discussion with the patient and the ophthalmologist, dulaglutide was restarted at 1.5 mg once weekly. After 4 weeks of reinitiation, the patient denied any recurrent symptoms of vitreous hemorrhage or worsening diabetic retinopathy. The most recent ophthalmology evaluation indicated no change in diabetic retinopathy. Practice implicationsThis case report adds to the limited body of evidence available for the incidence of vitreous hemorrhage in the setting of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) therapy and pre-existing diabetic retinopathy. The case report illustrates that a history of diabetic retinopathy should not automatically preclude the use of GLP-1 RAs.

Real-World Evaluation of GLP-1 Receptor Agonist Therapy Persistence, Adherence and Therapeutic Inertia Among Obese Adults with Type 2 Diabetes.

In type 2 diabetes (T2D), key barriers to optimal glycaemic control include lack of persistence with treatment, reduced medication adherence and therapeutic inertia. This study aimed to assess the impact of these barriers in obese adults with type 2 diabetes treated with a GLP-1 receptor agonist (GLP-1RA) and compare them against other glucose-lowering agents in a real-world setting. A retrospective study was conducted using electronic medical records from 2014 to 2019 for adults with T2D at the ValenciaClínico-Malvarrosa Department of Health (Valencia,Spain). Four study groups were established: all GLP-1RA users, SGLT2i users, insulin users and other glucose-lowering agent users (miscellany group). To account for imbalance between groups, propensity score matching (PSM) including age, gender and pre-existing cardiovascular disease was performed. Chi-square tests were used for comparisons between groups. Time to first intensification was calculated using competing risk analysis. Among the 26,944 adults with T2D, 7392 individuals were selected following PSM, with 1848 patients in each group. At 2 years, GLP-1RA users were less persistent than non-users (48.4% versus 72.7%, p < 0.0001) but more adherent (73.8% versus 68.9%, respectively, p < 0.0001). A greater proportion of persistent GLP-1RA users than non-persistent users exhibited reduced HbA1c (40.5% versus 18.6%, respectively, p < 0.0001), but no differences in cardiovascular outcomes and death were found. Overall, therapeutic inertia was observed in 38.0% of the study population. The large majority of GLP-1RA users received treatment intensification, whereas only 50.0% of GLP-1RA non-users were intensified. Under real-life conditions, obese adults with T2D persistently treated with GLP-1RA showed improved glycaemic control. Despite benefits, persistence with GLP-1RA was limited after 2 years. Additionally, therapeutic inertia occurred in two out of three study participants. Strategies to facilitate medication adherence, persistence and treatment intensification in people with T2D should be made a priority in order to achieve and maintain glycaemic targets and improve outcomes in this population. Study registered in clinicaltrials.org with the identifier NCT05535322.

Retrospective Analysis of Hospitalized Patients with Type 2 Diabetes Mellitus Treated with Glucagon-Like Peptide 1 Receptor Agonist Therapy.

The use and overall benefit of glucagon-like peptide-1 (GLP-1) receptor agonist therapy for hospitalized patients with type 2 diabetes mellitus (DM) with chronic kidney disease (CKD) has limited data regarding impact and safety. We studied the impact and safety of GLP-1 receptor agonist therapy in hospitalized DM patients with CKD. Retrospective study of 51 patients using either dulaglutide (n = 3) or liraglutide (n = 48). Glomerular filtration rate (GFR) groups of stages 3 to 5 and 1 and 2 were compared. The primary outcome was total amount of insulin within the last 24 hours in the hospital. The secondary outcomes were glucose management and safety. Mean insulin total amount within the last 24 hours in the hospital significantly differed (P = 0.01) between the GFR groups, with the GFR stages 3 to 5 group (mean 0.5, standard deviation 0.36) having a lower mean insulin level than the GFR stages 1 and 2 group (mean 0.8, standard deviation 0.45). Point-of-care glucose reached the target of 140 to 180 mg/dL within the last 24 hours in hospital, with increased odds for the GFR stages 3 to 5 group as compared with the GFR stages 1 and 2 group (odds ratio 4.08, 95% confidence interval 1.05-15.83, P = 0.04). For both GFR groups, there were minimal adverse events. Almost all of them continued GLP-1 receptor agonist therapy at discharge (94.1%). The use of GLP-1 receptor agonist therapy had better outcomes in patients with GFR stages 3 to 5 as compared with GFR stages 1 and 2. There were minimal adverse events reported for both GFR groups. This study suggests that the off-label use of GLP-1 receptor agonists for hospitalized DM patients with CKD may be useful.