Dulaglutide Therapy Research Articles

Dulaglutide rescues the elevated testicular dysfunction in a mouse model of high-fat diet-induced obesity

Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells. We used a well-known animal model of high-fat diet-induced obesity in this investigation, and testicular dysfunction was determined by sperm DNA damage, spermatocyte chromosomal abnormalities, and spermiogram analysis. Following a 12-week high-fat diet challenge, mice were randomly assigned to dulaglutide (0.6 mg/kg/day) or saline treatments for five weeks. Testes and sperm cells were collected 24 h after the last dulaglutide injection. Untreated obese mice had a lower testes/body weight ratio, more sperm DNA damage, diakinesis-metaphase I chromosomal abnormalities, a lower sperm count/motility, more cell morphological defects, and an altered testicular redox balance. In obese mice, dulaglutide injection efficiently restored all disturbed parameters to their control levels. Dulaglutide injection into healthy mice exhibited no significant harmful effects at the applied regimen. As a result, we infer that dulaglutide therapy might bring obese men additional benefits by recovering testicular dysfunction induced by obesity.

Efficacy and Safety of Injectable Dulaglutide 1.5 mg Among Type 2 Diabetes Patients in Clinics at King Saud Medical City, Riyadh, Saudi Arabia

IntroductionType 2 diabetes mellitus is the most common type of diabetes, characterized by varying degrees of insulin resistance and diminishing beta-cell function, which increases the risk of macrovascular and microvascular complications. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is administered once weekly and approved for treating adults with type 2 diabetes mellitus. It can be used as a monotherapy or in addition to oral hypoglycemic or insulin therapy.AimThis study aims to provide information contributing to assessing the efficacy and safety of weekly 1.5 mg dulaglutide therapy in Saudi adult patients with type 2 diabetes mellitus.MethodsA retrospective single-arm cohort study using a purposive sample to recruit type 2 diabetes mellitus patients on dulaglutide from endocrine and diabetic outpatient clinics in King Saud Medical City (N = 205). Data were collected from participants’ medical profiles and through the phone using interview questionnaires.ResultsMost participants were female and married; approximately 33% had had diabetes for more than 20 years, 41.4% of the sample had third-class obesity, and more than half had used dulaglutide for the last 1–2 years. With therapy, weight, body mass index, hemoglobin A1c, and fasting blood sugar were significantly improved after 6 and 12 months from baseline. The main side effects reported were nausea (52%) and fatigue (28%).ConclusionDulaglutide is a safe and effective therapy that demonstrated favorable glycemic control and weight reduction in obese type 2 diabetes patients of Saudi origin.

Assessment of Changes in Body Composition After 3 Months of Dulaglutide Treatment.

Changes in body composition accompanied by glucagon-like peptide 1 receptor agonist (GLP-1RA) induced weight loss have drawn much attention. However, fewer studies have reported body composition changes in patients receiving dulaglutide therapy in Chinese population. A total of 70 overweight/obese type 2 diabetes mellitus (T2DM) patients who received dulaglutide therapy were included. Clinical data were collected. Visceral fat area (VFA) and body composition were also measured. Changes in clinical indicators and body composition of patients before and after intervention were also analyzed. Correlation analysis and multiple linear regression model were used to evaluate the association between hemoglobin A1C (HbA1c) and body composition. The results showed that body weight (BW), VFA, body fat (BF), lean body mass (LBM), skeletal muscle mass (SMM) and water content were reduced after 3 months dulaglutide intervention. The lean body mass percentage (LBMP) and skeletal muscle mass percentage (SMMP) significantly increased. Moreover, there was no significant difference in bone mineral quality (BMQ) after the intervention. The multiple linear regression model revealed that the % change in BF was independently associated with % change in HbA1c (β = 0.449, t = 3.148, p=0.002). These results indicate that dulaglutide intervention does not cause muscle and bone mass loss while inducing weight loss, and % change in BF was independently associated with improved glucose control during dulaglutide therapy. This study offers some positive results to support the clinical application of dulaglutide.

Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.

Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3mg/kg dulaglutide group (Low Dula group), and a CMS+0.6mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

Comparison of Effects of Injectable Semaglutide and Dulaglutide on Oxidative Stress and Glucose Variability in Patients with Type 2 Diabetes Mellitus: A Prospective Preliminary Study.

Recent trials have shown that glucagon-like peptide-1 receptor agonists considerably reduce atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Oxidative stress, a surrogate marker of cardiovascular risk, is associated with glucose variability. However, to the best of our knowledge, no studies have compared the effects of injectable semaglutide and dulaglutide therapies on oxidative stress and glucose variability assessed via continuous glucose monitoring (CGM). This study aimed to analyze and compare the effects of semaglutide and dulaglutide therapies on oxidative stress and glucose variability as assessed through CGM. This is an open-label, multicenter, randomized, prospective, parallel-group comparison study. Overall, 37 patients with T2DM treated with dulaglutide for at least 12weeks were randomized into two groups: one receiving continuous dulaglutide therapy (n = 19) and one receiving injectable semaglutide therapy (n = 18) groups. The coprimary endpoints were changes in the results of the diacron-reactive oxygen metabolites test, an oxidative stress marker, and CGM-evaluated glucose variability after 24weeks. The secondary endpoint was changes in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores. Switching to semaglutide therapy was better than continuous dulaglutide therapy in reducing oxidative stress, glucose variability, and glycated hemoglobin levels. Conversely, continuous dulaglutide therapy was better than semaglutide therapy in terms of DTSQ scores for "Convenience" and "Recommend." Injectable semaglutide therapy may be more effective than dulaglutide therapy in ameliorating oxidative stress and regulating glucose metabolism, including glucose variability, in patients with T2DM, while dulaglutide therapy may be more effective in terms of treatment satisfaction. UMIN-CRT ID: UMIN000042670 (registered 7 December 2020).

FRI657 Case Series On GLP-1 Receptor Agonist Related Acute Pancreatitis

Abstract Disclosure: A.U. Kulkarni: None. V. Mehta: None. M. Renzu: None. K. Pereira: None. M.A. Rather: None. Introduction: Acute pancreatitis (AP) has now become one of the leading causes of GI related hospital admissions in the United States. With increasing use of GLP-1 Receptor Agonists (GLP-1 RA) in T2DM and obesity, they are now being identified as one such class of drugs which can cause AP. We present this case series to discuss these adverse effects. Case 1: A 50 yo AA male with a history of T2DM and hypertension presented with acute severe epigastric pain, nausea and vomiting for 5 days. Vitals were stable. On physical exam, tenderness in the RUQ was noted. Labs revealed lipase of 313 U/l (11-82 U/l), BG of 213 mg/dL, HbA1c 11.3, normal LFT and lipid panel. Blood EtOH was negative. He denied tobacco, alcohol, and illicit drug use. CT abdomen showed acute interstitial edematous pancreatitis without cholelithiasis or choledocholithiasis. Liver ultrasound showed hepatic steatosis. He noted recent initiation of Semaglutide 6 months ago which was stopped 3 weeks prior to this visit due to abdominal discomfort. Previous Dulaglutide therapy was also discontinued due to GI intolerance. Home medication for DM otherwise included metformin and basal insulin. Case 2: A 68 yo AA woman with a history of T2DM, hypothyroidism presented after a week of severe epigastric pain, radiating to her back, with nausea and vomiting. Labs showed lipase 593 U/l (11-82 U/l), BG of 427 mg/dl, HbA1c of 10. Social history was non-contributory. CT Abdomen showed AP and no gallstones or bile duct dilatation. LFTs and lipid panel were unremarkable. Chart review noted prior admission for AP a month ago. Her home medications were basal Insulin and Dulaglutide (4 yrs). Drug induced AP from Dulaglutide was suspected. Lack of clinical improvement after 3 days of management prompted RUQ ultrasound, which was prematurely terminated due to pain during the scan. Subsequent CCK-HIDA was negative for acute cholecystitis but noted low gallbladder EF. Thus dulaglutide was identified as a potential trigger along with gallbladder dysmotility as a possible etiology for her recurrent AP. Both patients were managed with IV fluids, NPO diet and morphine. They were instructed to stop GLP-1 RA and discharged with PCP follow-up. Discussion: GLP-1 RA are now being widely used due to low risk of hypoglycemia and weight loss. Clinical trials with GLP-1 RA have shown mild, asymptomatic increase in lipase, amylase levels as well as rare incidences of AP. This has been attributed to the stimulation of pancreatic beta cells and exocrine duct cells leading to acinar cell hypertrophy, proinflammatory cytokine induction, causing pancreatic injury. Though drug-induced AP is uncommon and is a diagnosis of exclusion, detailed history taking, medication review and investigating for all other causes is of utmost importance. A good understanding of the drugs associated with AP should alert the physician to identify these agents and promptly discontinue them to prevent further complications. Presentation: Friday, June 16, 2023

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.

768-P: Effect of Dulaglutide Therapy Initiation on the Course of Coronavirus Infection and the Dynamics of Inflammatory Markers in Hospitalized Patients with Type 2 Diabetes

Aim: To determine the impact of initiation of dulaglutide therapy on the course of COVID-19 and the dynamics of inflammatory markers in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods: The inclusion criteria were history of T2DM, BMI > 27 kg/m2, PCR-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. In both groups we compared COVID-19 outcomes (mortality/survival rate, ICU admission, need for assisted ventilation) and the duration of hospitalization. On days 3 and 7 of hospitalization we assessed laboratory parameters (FPG, CRP, ALT, AST, LDH, lymphocyte levels, D-dimer). Results: The initiation of dulaglutide therapy reduced the risk of death and transfer to assisted ventilation by 3.5 times in the intervention group compared to the control one (5.7% vs 20.0%, p=0.038). No differences were found in the risk of ICU admission (17.0% vs 28.0%, p=0.18) and the duration of hospitalization (10 bed-days vs 11-bed days, p=0.26). The groups were comparable in respect to carbohydrate metabolic compensation. Compared to those in the control group, patients on dulaglutide therapy demonstrated a lower CRP level (15.8 vs 24.6 mg/L, p=0.035), higher lymphocyte levels (1.2 vs 0.9 × 10*9/L, p=0.049) on day 3 of hospitalization, and a significantly lower LDH concentration level on day 7 (261.6 vs 326.1 U/L, p=0.016). There were no differences in ALT, AST, and D-dimer levels. Conclusion: The initiation of dulaglutide therapy in hospitalized patients with T2DM and COVID-19 decreased the risk of lethal outcomes and transfer to assisted ventilation, as well as proved effective in regards to inflammatory markers (CRP, lymphocytes levels). Disclosure T.Markova: None. M.Stas: None. A.Anchutina: None.

786-P: Effects of Switching from Liraglutide or Dulaglutide to Subcutaneous Semaglutide on Metabolic Parameters in Older People with Type 2 Diabetes Mellitus—SWITCH-SEMA1 Subgroup Analysis

Background: Once-weekly treatment with the subcutaneous glucagon-like receptor-1 receptor agonist (GLP-1RA) semaglutide has been reported to have potent beneficial effects on metabolic abnormalities. However, little is known about the usefulness of switching from other GLP-1RAs to semaglutide, especially in older people with type 2 diabetes. Methods: This study is a subgroup analysis of the SWITCH-SEMA1 study, a multicenter, prospective, open-label, parallel-group, randomized controlled study in which people with type 2 diabetes continued liraglutide or dulaglutide therapy or switched to semaglutide for 24 weeks (jRCTs1011200008). One hundred people enrolled in this study were divided into two groups: an aged group consisting of people 65 years or older (n = 49; 72.8 ± 4.4 years old) and a non-aged group (n = 51; 51.2 ± 6.8 years old). The changes of metabolic parameters between the two treatment arms (continuation vs switching to semaglutide) were compared between an aged and a non-aged group. Results: At baseline, BMI, fatty liver index (FLI), C-peptide index (CPI), HOMA2-β, HOMA2-R, eGFR, and triglyceride levels were significantly lower in the aged group (all P < 0.05). After 24 weeks, switching to semaglutide significantly ameliorated HbA1c in both groups (aged: −0.7%, P<0.001; non-aged: −0.7%, P < 0.01). In the aged group, FLI; CPI; HOMA2-β; AST, γ-GTP, and uric acid (UA) levels; and the Diabetes Treatment Satisfaction Questionnaire (DTSQ) score significantly improved after switching to semaglutide (all P < 0.05). The magnitude of changes in BMI and UA levels after switching to semaglutide was greater in the aged group than in the non-aged group (BMI: −1.1 vs. −0.5 kg/m2, P < 0.01; UA: −0.4 vs. −0.1 mg/dL, P <0.05). Conclusions: The effects on metabolic parameters of switching from other GLP-1RAs to once-weekly semaglutide might be greater in aged people than in non-aged people. Disclosure Y.Takahashi: None. H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. H.Yokoyama: None. A.Miya: None. A.Miyazaki: None. H.Kameda: None. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. H.Miyoshi: Research Support; Abbott, LifeScan Diabetes Institute, Taisho Pharmaceutical Holdings Co., Ltd., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Kowa Company, Ltd., MSD Life Science Foundation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation.

1479-P: Targeted Exome Sequencing for Long-Term Efficacy and Weight Loss of Dulaglutide in Type 2 Diabetes

Introduction: There are individual differences in glucose lowering effect and weight reduction of dulaglutide, long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is expected that genetic variations in the mechanism of action of drugs are involved in treatment response to drugs. This study aims to investigate genetic variants associated with long-term efficacy and weight reduction of dulaglutide using targeted next-generation sequencing. Methods: We recruited 77 patients those who were treated with dulaglutide at least one year after switching from DPP-4 inhibitors (±basal insulin) due to uncontrolled type 2 diabetes (HbA1c ≥8.0%) at Korean VHS medical center between September 2018 and October 2019, and followed up until March 2021. The responder was defined by ≥1.0% HbA1c reduction at 24 weeks and achievement of HbA1c ≤7.5% at 52 weeks. We designed targeted exome panel based on the mechanism of drug action, and candidate genetic variants included known GLP-1 response related genes (n=10), gastric emptying related genes (n=18), pancreatic insulin secretion related genes (n=25). At the same time, we also performed whole exome sequencing. Results: During follow-up period of median 2.5±1.3 years, HbA1c was 9.7±1.3% at baseline and reduced to 8.2±1.5% at 6 months, and maintained thereafter up to 4 years. Glycemic response was associated with GNB3, SPARC, and COL4A1 genes. Weight loss (n=13) was more frequently observed in patients with minor G alleles of COL4A1 gene (OR 2.516, 95% CI 1.013, 6.249, p=0.047). Glycemic effectiveness of dulaglutide therapy is associated with genetic variants (OR 2.106, 95% CI 1.358, 3.265, p=0.001) as well as baseline HbA1c (OR 1.682, 95% CI 1.067, 2.650, p=0.025). Conclusion: The glucose lowering effect of dulaglutide, which exempts some patients from insulin therapy, has been associated with GNB3, SPARC, and COL4A1 variants. Polymorphisms in COL4A1 gene was associated with weight loss, although further studies are needed for validation. Disclosure Y.Kim: None. J.Seo: None. Funding VHS Medical Center (VHSMC20026)

Glucagon-like peptide-1 therapy for youth with type 2 diabetes.

Glucagon-like peptide-1 therapy for youth with type 2 diabetes.

P15.05: Safety of Once-Weekly Dulaglutide on Post-transplant Diabetes Mellitus: A Preliminary Single-Centre Experience

Introduction: Almost all immunosuppressive drugs (IS), including glucocorticoids, calcineurin and mTOR inhibitors, play a central role in the development of Post-Transplant Diabetes Mellitus (PTDM). IS potentially cause the development of a dysglycemic state, both for the direct cytotoxic action on pancreatic beta cells and for the induction of insulin resistance. PTDM is also associated with increased risk for cardiovascular disease and with worse graft and patients’ survival. Currently there are no clear recommendations on the choice of the most safe and effective anti-diabetic drug for PTDM. IS are linked with several pharmacokinetic interactions and burdened with vary degree of nephrotoxicity. Glucagon like peptide- 1 receptor agonists (GLP1RA) are largely used for the treatment of type 2 diabetes. They act stimulating endogenous insulin secretion in a glucose-dependent manner. GLP1RAs reduce blood sugar by stimulating insulin release, suppressing high glucagon levels, delaying gastric emptying, and reducing food intake. Furthermore, GLP1 has been shown to promote proliferation of beta cells in animal models. GLP1RA has proven to be safe and effective in reducing HbA1c without directly causing hypoglycemia and has shown a clear association with cardiovascular risk reduction and renal protection. Despite GLP1RA seems to act with a mechanism that perfectly contrasts the pathogenetic aspects of PTDM, in the literature clinical experience is entirely limited to case series and retrospective studies. Method: In order to assess primarily safety of GLP1RA therapy in patients with PTDM we have prospectively enrolled a sample of N = 20 patients referred to liver (N = 10), renal (N = 5), as well as heart (N = 4) and lung (N = 1) transplant at ISMETT. All patients were placed on once-weekly dulaglutide therapy. Weight, HbA1c Level, as well as complete lipid profile and liver function tests were performed at 3 months and again at 6 months. One-way Repeated measurements ANOVA was used to test significant change in collected variables over time. Results: The study was closed at 6 months follow-up visit. Mild gastrointestinal symptoms were experienced by patients at the treatment start and resolved in 2 weeks. There were no persistent side effects due to dulaglutide in our study population and all recruited patients were on dulaglutide at 6 months evaluation. Body weight, Total cholesterol, Fibrosis-4 Index, alanine aminotransferase and aspartate aminotransferase levels were all reduced at the end of the follow-up, while blood glucose as well as HbA1c were stable over time (Table 1, Figure 1). Conclusion: Dulaglutide has proven to be safe in a population of transplanted patients with PTDM. In addition, a significative reduction of metabolic parameters was found. GLP1RA could be a preferred treatment for patients with PTDM considering also the extraglycemic effects of cardiovascular and renal protection.

Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes

BackgroundThe incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes.MethodsIn a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75 mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75 mg. The primary end point was the change from baseline in the glycated hemoglobin level at 26 weeks. Secondary end points included a glycated hemoglobin level of less than 7.0% and changes from baseline in the fasting glucose concentration and BMI. Safety was also assessed.ResultsA total of 154 participants underwent randomization. At 26 weeks, the mean glycated hemoglobin level had increased in the placebo group (0.6 percentage points) and had decreased in the dulaglutide groups (–0.6 percentage points in the 0.75-mg group and −0.9 percentage points in the 1.5-mg group, P<0.001 for both comparisons vs. placebo). At 26 weeks, a higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated hemoglobin level of less than 7.0% (51% vs. 14%, P<0.001). The fasting glucose concentration increased in the placebo group (17.1 mg per deciliter) and decreased in the pooled dulaglutide groups (−18.9 mg per deciliter, P<0.001), and there were no between-group differences in the change in BMI. The incidence of gastrointestinal adverse events was higher with dulaglutide therapy than with placebo. The safety profile of dulaglutide was consistent with that reported in adults.ConclusionsTreatment with dulaglutide at a once-weekly dose of 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control through 26 weeks among youths with type 2 diabetes who were being treated with or without metformin or basal insulin, without an effect on BMI. (Funded by Eli Lilly; AWARD-PEDS ClinicalTrials.gov number, NCT02963766.)

Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy.

AimsGlucagon‐like peptide 1 (GLP-1) receptor agonists have demonstrated strong glycemic control. However, few studies have investigated the effects of switching from insulin to GLP-1 receptor agonists. We aimed to investigate, using real-world data, whether switching to dulaglutide improves glycemic control in patients with type 2 diabetes mellitus (T2D) inadequately controlled with conventional insulin treatment.Materials and methodsWe retrospectively evaluated 138 patients with T2D who were switched from insulin to dulaglutide therapy. We excluded 20 patients who dropped out during the follow-up period. The participants were divided into two groups according to whether they resumed insulin treatment at 6 months after switching to a GLP-1 receptor agonist (group I) or not (group II). A multiple logistic regression analysis was performed to evaluate the parameters associated with the risk of resuming insulin after replacement with dulaglutide.ResultsOf 118 patients initiated on the GLP-1 receptor agonist, 62 (53%) resumed insulin treatment (group I), and 53 (47%) continued with GLP-1 receptor agonists or switched to oral anti-hypoglycemic agents (group II). Older age, a higher insulin dose, and lower postprandial glucose levels while switching to the GLP-1 receptor agonist were associated with failure to switch to the GLP-1 receptor agonist from insulin.ConclusionsA considerable proportion of patients with T2D inadequately controlled with insulin treatment successfully switched to the GLP-1 receptor agonist. Younger age, a lower dose of insulin, and a higher baseline postprandial glucose level may be significant predictors of successful switching from insulin to GLP-1 receptor agonist therapy.

The effect of Dulaglutide on glycemic and weight control in patients with type 2 diabetes.

The objectives of type 2 diabetes treatment are to achieve adequate long-term glycemic control and to reduce the risk associated with comorbidities and complications. Once-weekly Dulaglutide showed a reduction in cardiovascular risk associated with diabetes in addition to improved glycemic control and bodyweight reduction in several clinical trials. We aimed to investigate the effect of Dulaglutide 1.5 mg on glycemic and weight control in type 2 diabetes patients inadequately controlled by antihyperglycemic treatment in real-world clinical practice. We retrospectively reviewed the medical records of 50 patients with type 2 diabetes inadequately controlled by previous treatment and newly initiated on Dulaglutide. The data were collected at 6 months (n=50) and 12 months (n=40) after Dulaglutide therapy initiation. Dulaglutide treatment resulted in significant improvement of glycated hemoglobin (-1.3 %; p<0.001) after 6 months and after 12 months (-2.0 %; p<0.001). Significant bodyweight reduction was found after 6 months (-2.0 kg; p=0.002) and 12 months (-3.5 kg; p=0.001) of Dulaglutide treatment initiation. In addition, a reduction in insulin dose was observed. Our clinical data showed that Dulaglutide 1.5 mg significantly improved glycemic and bodyweight control at 6 and 12 months after treatment initiation in patients with type 2 diabetes inadequately controlled by previous antihyperglycemic treatment.

Association of Dulaglutide Initiation Timing With Treatment Patterns and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus in the United States

PurposeTo describe clinical characteristics and treatment outcomes for early or late initiation of dulaglutide therapy in patients with type 2 diabetes. MethodsThis retrospective, claims-based analysis evaluated adults with type 2 diabetes, ≥1 claim for dulaglutide 0.75 mg or 1.5 mg once-weekly injection (between November 2014 and August 2019), and no prior use of glucagon-like peptide 1 receptor agonists or insulin. Cohorts were defined based on the number of oral antidiabetic drug (OAD) classes used within the 24-month baseline period before dulaglutide therapy initiation: 1 OAD, 2 OADs, or ≥3 OADs. The number of OAD classes used before dulaglutide therapy initiation served as a proxy for timing of initiation, with a higher number of OAD classes indicating a longer duration of T2D. Baseline demographic and clinical characteristics were compared across each cohort. Six-month follow-up outcomes, including change in glycosylated hemoglobin (HbA1c) and treatment patterns, were descriptively assessed within each cohort. FindingsThe study population consisted of 18,121 patients across the 1 OAD (n = 4822), 2 OADs (n = 6293), and ≥3 OADs (n = 7006) cohorts. Mean age at baseline was 54.7 years. Males were more prevalent in the ≥3 OADs cohort. Most patients (67%–70%) initiated treatment with dulaglutide 0.75 mg. Dose escalation to 1.5 mg was uncommon (15%–20%) but trended higher in the ≥3 OAD cohort. Adherence to dulaglutide at 6-month follow-up (61%–67%) increased with higher baseline OAD use. The HbA1c assessment (n = 3178) included 761 patients in the 1 OAD cohort, 1088 patients in the 2 OADs cohort, and 1329 patients in the ≥3 OADs cohort. Baseline mean [SD] HbA1c level increased with number of OAD classes (1 OAD: 8.18% [1.80]; 2 OADs: 8.56% [1.66]; and ≥3 OADs: 8.73% [1.51]). Patients in the early dulaglutide therapy initiator group experienced larger reductions in HbA1c levels (1 OAD: −1.39%; 95% CI, −1.50 to −1.27; 2 OADs: −1.30%; 95% CI, −1.39 to −1.20; and ≥3 OADs: −1.01%; 95% CI, −1.09 to −0.93) versus the patients in the delayed initiator group. Patients in the early dulaglutide therapy initiator group also achieved HbA1c <7% at 6-month follow-up more frequently than those in the later initiator group (1 OAD: 68%; 2 OADs: 51%; and ≥3 OADs: 33%). ImplicationsCohorts of dulaglutide therapy initiators, defined by prior OAD use as a proxy of timing of initiation, differed in their baseline characteristics and short-term follow-up outcomes. Earlier dulaglutide therapy initiation was associated with lower mean HbA1c levels and increased probability of achievement of HbA1c <7% during the 6-month follow-up period.

Switching from insulin to dulaglutide therapy in patients with type 2 diabetes: A real-world data study.

Patients with type 2 diabetes (T2DM) who require injectable therapy have been conventionally treated with insulin. A glucagon-like peptide 1 receptor agonist was recently recommended as first-line injectable treatment, but few studies have investigated the effects of switching from insulin to dulaglutide. This study investigated the clinical efficacy and parameters affecting responses to dulaglutide as an alternative to insulin in patients with T2DM in a real-world clinical setting. Ninety-eight patients with T2DM who were switched from insulin to dulaglutide therapy were retrospectively evaluated. Changes in HbA1c concentrations were assessed after 6 months of consistent treatment with dulaglutide. Multiple linear regression analysis was performed to evaluate parameters affecting the response to dulaglutide treatment. After treatment with dulaglutide for 6 months, patients experienced changes in HbA1c of -0.95% (95% confidence interval [CI]: -1.30% to -0.59%, P<0.001) and in body weight of -1.75 kg (95% CI: -2.42 to -1.08 kg, P<0.001). Multiple linear regression analysis showed that higher baseline HbA1c was significantly associated with a greater reduction in HbA1c. The most frequent adverse events were gastrointestinal symptoms. Switching from insulin to dulaglutide can lead to significant improvement in HbA1c levels and body weight ​reduction in T2DM patients over 6 months. Higher baseline HbA1c is associated with a better clinical response to dulaglutide.

Real-World Efficacy and Safety of Dulaglutide in Korean Patients with Type 2 Diabetes Mellitus: A Retrospective Study in a Tertiary Referral Center.

This study was conducted to evaluate the efficacy and safety of once-weekly dulaglutide therapy as add-on to oral antidiabetic drugs (OADs) and basal insulin in Korean patients with type 2 diabetes mellitus (T2DM) in real-world clinical practice. We retrospectively reviewed the medical records of 112 patients who received dulaglutide in a tertiary referral center. The primary efficacy endpoint was a change in glycated hemoglobin (HbA1c) between baseline and 6 months. The secondary endpoints were the percentage of patients achieving HbA1c <7.0% or ≤6.5% and the change of body weight at 6 months. At baseline, the mean HbA1c was 8.7 % (8.8% in the OAD combination and 8.5% in the basal insulin combination group). The mean adjusted HbA1c at 6 months decreased by −1.13% in all patients (p<0.001), and by −1.36 and −0.74% in the OAD combination and basal insulin combination group, respectively. A significant reduction of −2.9 kg in body weight was observed in all patients at 6 months (p<0.001). Approximately 34.8% and 23.2% of patients achieved HbA1c <7.0% and ≤6.5%, respectively. Higher baseline HbA1c and no previous insulin therapy were associated with positive responses to dulaglutide on multivariate analysis. Mild gastrointestinal issues (23.2%) were the most frequently observed adverse events. Dulaglutide is an effective and durable treatment option as OAD and basal insulin combination therapy in Korean patients with T2DM.

Elderly Diabetic Patients with Effective Add-on Therapy of Dulaglutide as a GLP-1 Receptor Analogue (GLP-1 RA)

Background: For diabetic treatment, Dulaglutide has been used and effective as a glucagon-like peptide-1 receptor analogue (GLP-1 RA). This report is to describe the various responses and to analyze dulaglutide administration in the elderly with DM. Case presentation: Two patients were Type 2 Diabetes Mellitus (T2DM) treated with add-on therapy of Dulaglutide. Case 1 is 81-year-old female is diabetic for 2 years, and on Metformin and Glimepiride as Oral Hypoglycemic Agents (OHAs). Her HbA1c was higher with 10.6% and she was started to given Dulaglutide 0.75mg. Remarkable efficacy was found in 3 months with HbA1c 6.7%. Value of LDL-C increased from 135 mg/dL to 158 mg/dL. Case 2 is 83-year-old male with 27 years of diabetes. He was on medication of Metformin and Glimepiride. His HbA1c persisted around 9.0%-9.4%, then he was provided Dulaglutide as add-on therapy. In 3 months, HbA1c decreased to 8.2% and LDL-C increased from 57 mg/dL to 116 mg/dL. Discussion and conclusion: Dulaglutide is a useful GLP-1 RA with once a week administration. There were some reports concerning LDL changes after dulaglutide therapy, showing that the changes may depend on the basal LDL value before the administration of dulaglutide. Dulaglutide may influence lipid metabolism. This report is expected to become reference in diabetic practice and research in the future.

1113-P: The Use of Empagliflozin and Dulaglutide Improves Metabolic and Glycemia Outcomes in a Real-World Primary Care Setting

Improving key metabolic parameters in patients with type 2 diabetes can be challenging in primary care, and integration of diabetes services within the community plays a vital role. GLP-1 receptor agonists and SGLT2 inhibitors are effective at improving glycemic control and weight, and once weekly GLP-1 receptor agonists can improve the adherence to therapy. In this retrospective observational study, we examined the outcomes in primary care practices within the West Berkshire Clinical Commissioning Group. Methods: We identified 313 patients who had been started on a combination of dulaglutide and empagliflozin (either exclusively or as an add-on). Clinical and metabolic parameters (HbA1c, weight, blood pressure, ALT, cholesterol and eGFR) were measured prior to, and at 3, 6 and 12 months after the start of dual treatment. The study population characteristics were as follows: 57% male, age (mean +/- SD) 57 +/-9 years, HbA1c 9.5 +/- 1.6% (80 +/- 17.5 mmol/mol), weight 106.1 +/- 22 kg. Repeated measures ANOVA was used to compare values to baseline. Results: HbA1c decreased to 8.3% (67mmol/mol) at 3 months and to 8.1% (65mmol/mol) at 12 months (p&amp;lt;0.001); weight decreased by 2.5kg at 3 months and by 5.7kg at 12 months (p&amp;lt;0.001). Blood pressure decreased from 131 to 128mmHg systolic and from 78 to 77mmHg diastolic (p&amp;lt;0.005) at 3 months. ALT decreased from 36.3 to 31.1mmol/L at 3 months and to 29.9mmol/L at 12 months (p&amp;lt;0.001), cholesterol decreased from 4.4 to 4.2mmol/L at 3 months (p=0.005), while eGFR decreased slightly from 79.9 mean to 78 at 3 months (p&amp;lt;0.001). Conclusion: In this real-world, primary care study of patients with difficult to manage diabetes and increased weight, the use of empagliflozin plus once weekly dulaglutide therapy led to an improvement in glycemic control and other metabolic parameters, and a reduction in weight. These effects could be observed within 3 months of starting dual therapy, and were either maintained or further improved by 12 months. Disclosure I. Spiliotis: None. I.W. Gallen: None.