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1.
Cardiovasc Diabetol ; 23(1): 166, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38730425

ABSTRACT

BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.


Subject(s)
Antihypertensive Agents , Blood Glucose , Blood Pressure , Diabetes Mellitus, Type 2 , Genetic Predisposition to Disease , Glycemic Control , Guanine Nucleotide Exchange Factors , Polymorphism, Single Nucleotide , Humans , Male , Female , Middle Aged , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/adverse effects , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/blood , China/epidemiology , Blood Glucose/metabolism , Blood Glucose/drug effects , Aged , Retrospective Studies , Guanine Nucleotide Exchange Factors/genetics , Risk Factors , Treatment Outcome , Glycemic Control/adverse effects , Blood Pressure/drug effects , Blood Pressure/genetics , Asian People/genetics , Diabetic Angiopathies/genetics , Diabetic Angiopathies/diagnosis , Risk Assessment , Phenotype , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Time Factors , Biomarkers/blood , Genetic Association Studies , Hypertension/genetics , Hypertension/drug therapy , Hypertension/physiopathology , Hypertension/diagnosis , DNA-Binding Proteins/genetics , East Asian People
2.
BMJ Case Rep ; 17(5)2024 May 06.
Article in English | MEDLINE | ID: mdl-38719260

ABSTRACT

The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.


Subject(s)
CA-19-9 Antigen , Diabetes Mellitus, Type 2 , Glucagon-Like Peptides , Hypoglycemic Agents , Immunoglobulin Fc Fragments , Recombinant Fusion Proteins , Humans , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Glucagon-Like Peptides/analogs & derivatives , Glucagon-Like Peptides/adverse effects , Glucagon-Like Peptides/therapeutic use , Female , Immunoglobulin Fc Fragments/adverse effects , Immunoglobulin Fc Fragments/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , CA-19-9 Antigen/blood , Middle Aged , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/blood
3.
PLoS One ; 19(5): e0302155, 2024.
Article in English | MEDLINE | ID: mdl-38701096

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucagon-Like Peptides , Glucosides , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/complications , Glucosides/therapeutic use , Glucosides/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Glucagon-Like Peptides/therapeutic use , Benzhydryl Compounds/therapeutic use , Benzhydryl Compounds/adverse effects , Middle Aged , Male , Double-Blind Method , Female , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Adult , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Drug Therapy, Combination , Blood Glucose/metabolism , Aged , Treatment Outcome
5.
Pharmacoepidemiol Drug Saf ; 33(5): e5800, 2024 May.
Article in English | MEDLINE | ID: mdl-38719731

ABSTRACT

PURPOSE: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Metformin , Pancreatitis , Sulfonylurea Compounds , Humans , Benzhydryl Compounds/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Pancreatitis/chemically induced , Pancreatitis/epidemiology , Glucosides/adverse effects , Glucosides/therapeutic use , Glucosides/administration & dosage , Sulfonylurea Compounds/adverse effects , Sulfonylurea Compounds/therapeutic use , Male , Female , Middle Aged , Aged , Metformin/adverse effects , Metformin/administration & dosage , Metformin/therapeutic use , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/administration & dosage , Databases, Factual , Incidence , Product Surveillance, Postmarketing/statistics & numerical data , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Adult , United States/epidemiology , Propensity Score
6.
Eur Rev Med Pharmacol Sci ; 28(8): 3073-3084, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38708466

ABSTRACT

OBJECTIVE: The aim of this study was to investigate and evaluate the risk of dyspepsia and anorexia in patients with type 2 diabetes mellitus (T2DM) induced by glucagon-like peptide 1 receptor agonist (GLP-1 RA) hypoglycemic drugs. MATERIALS AND METHODS: We searched papers in PubMed, Web of Science, Cochrane Library, Google Scholar, CNKI, Wanfang, Embase, and VIP databases, and the retrieval time limit was set from the establishment of the database to May 2023. Randomized Controlled Trials (RCTs) were collected in which the subjects were T2DM patients, the intervention was GLP-1RA compared with placebo or traditional hypoglycemic drugs, and the outcome indicators included dyspepsia and anorexia. A meta-analysis and a network meta-analysis were performed. RESULTS: The results of the traditional meta-analysis showed that the risk of dyspepsia and anorexia of total GLP-1 RA was 3.01 and 2.56 times that of placebo, respectively. All types of GLP-1RA were compared with placebo and the results also showed a trend towards increased risk of digestive system adverse events (DSAEs). Among all interventions included, liraglutide was the one with the highest risk of dyspepsia in patients with T2DM, and dulaglutide was the one with the highest risk of anorexia. CONCLUSIONS: The results of the two meta-analyses are consistent, and both clearly show that GLP-1RA can increase the risk of dyspepsia and anorexia in T2DM patients.


Subject(s)
Anorexia , Diabetes Mellitus, Type 2 , Dyspepsia , Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/complications , Glucagon-Like Peptide-1 Receptor/agonists , Dyspepsia/drug therapy , Dyspepsia/chemically induced , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Anorexia/chemically induced , Anorexia/drug therapy , Network Meta-Analysis , Randomized Controlled Trials as Topic
7.
Medicine (Baltimore) ; 103(18): e37928, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701264

ABSTRACT

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide are primarily used for managing blood sugar levels in type 2 diabetes and aiding weight loss. Typically, their adverse effects are gastrointestinal, with limited exploration into their impact on mental health. CASE PRESENTATION: This report examines a 39-year-old male with type 2 diabetes who developed depressive symptoms after starting liraglutide for glycemic control and weight reduction. Symptoms included poor mood, irritability, decreased interest and energy, progressing to sadness, low self-esteem, and physical discomfort. A clinical diagnosis of a depressive episode was made, coinciding with the initiation of liraglutide. INTERVENTION AND OUTCOME: The patient depressive symptoms significantly improved within a week after discontinuing liraglutide and starting antidepressant therapy. This suggests a possible link between liraglutide and depression, despite considering other factors like diabetes-related stress. DISCUSSION: The report explores potential mechanisms, such as GLP-1RA effects on glucose fluctuations and dopamine modulation, which might contribute to depressive symptoms. The influence on the brain reward system and the reduction in cravings for addictive substances after GLP-1RA use is also discussed as a factor in mood regulation. CONCLUSION: This case highlights the necessity of being vigilant about potential psychiatric side effects, particularly depression, associated with GLP-1RAs. The rarity of such reports calls for more research to investigate and understand these implications further.


Subject(s)
Depression , Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Liraglutide , Humans , Liraglutide/therapeutic use , Liraglutide/adverse effects , Male , Diabetes Mellitus, Type 2/drug therapy , Adult , Depression/drug therapy , Depression/chemically induced , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use
9.
J Assoc Physicians India ; 72(1): 32-42, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38736072

ABSTRACT

BACKGROUND: The efficacy and safety of lobeglitazone sulfate has been reported only in the Korean population, and no study has been conducted in India. MATERIALS AND METHODS: In this 16-week randomized, double-blind, and multicenter study, the efficacy and safety of lobeglitazone sulfate 0.5 mg were evaluated with pioglitazone 15 mg. Type 2 diabetes mellitus (T2DM) patients with ≥7.5% glycated hemoglobin (HbA1c) ≤10.5% and on stable metformin dose were assigned to both treatment arms. The primary outcome was a mean change in HbA1c. Safety assessments included adverse events (AE), home-based glucose monitoring, vital parameters, electrocardiogram (ECG), and laboratory assessments. RESULTS: A total of 328 subjects were randomized equally in two groups. A statistically significant reduction in HbA1c at week 16 in the lobeglitazone group with the least square (LS) mean change: 1.01 [standard error (SE): 0.09] (p < 0.0001) was seen. The LS mean difference between the two groups was 0.05 (SE: 0.12) [95% confidence interval (CI): -0.18, 0.27], which was statistically significant (p = 0.0013). Statistically significant reductions were also observed in fasting and postprandial glucose. Treatment-emergent Aes (TEAE) were comparable between both groups. CONCLUSION: Lobeglitazone 0.5 mg once daily was found to be efficacious and safe in the treatment of T2DM in the Indian population. Lobeglitazone significantly improved glycemic parameters and was noninferior to pioglitazone; hence, it could be a promising insulin sensitizer in T2DM management in India.


Subject(s)
Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Glycated Hemoglobin , Hypoglycemic Agents , Metformin , Pioglitazone , Thiazolidinediones , Humans , Diabetes Mellitus, Type 2/drug therapy , Metformin/therapeutic use , Metformin/administration & dosage , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Male , Middle Aged , Double-Blind Method , Female , Thiazolidinediones/therapeutic use , Thiazolidinediones/administration & dosage , Glycated Hemoglobin/analysis , India , Pioglitazone/therapeutic use , Pioglitazone/administration & dosage , Blood Glucose/analysis , Blood Glucose/drug effects , Adult , Treatment Outcome , Aged , Pyrimidines
10.
J Assoc Physicians India ; 72(1): 83-84, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38736078

ABSTRACT

Most of the cancer patients have multiple comorbid conditions, commonly diabetes mellitus, hypertension, and coronary vascular diseases. Cancer treatment involves a multidisciplinary approach targeting primary cancer-directed therapy along with optimal management of comorbid conditions as well. Hyperglycemia, which exists prior to cancer therapy initiation or if it develops during or after therapy, is associated with less desirable outcomes like treatment compromise due to increased adverse effects of therapy and higher mortality. Hence, prompt diagnoses and management of hyperglycemia become crucial during therapy. Healthcare providers working in an oncology setting, as well as primary care providers, should be aware of medications that are associated with hyperglycemia and diabetes. This paper will elucidate various cancer-directed therapies associated with hyperglycemia.


Subject(s)
Hyperglycemia , Neoplasms , Humans , Neoplasms/complications , Neoplasms/drug therapy , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Antineoplastic Agents/adverse effects
14.
J Diabetes ; 16(4): e13526, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38584148

ABSTRACT

BACKGROUND: Bexagliflozin and dapagliflozin are sodium-glucose cotransporter-2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. METHODS: This was a multicenter, randomized, double-blind, active-controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2-h-postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. RESULTS: The model-adjusted mean change from baseline to week 24 HbA1c was -1.08% for bexagliflozin and -1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] -0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were -1.95 mmol/L, -3.24 mmol/L, -2.52 kg, and -6.4 mm Hg in the bexagliflozin arm and -1.87 mmol/L, -3.07 mmol/L, -2.22 kg, and -6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. CONCLUSIONS: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin.


Subject(s)
Benzhydryl Compounds , Diabetes Mellitus, Type 2 , Glucosides , Metformin , Pyrans , Adult , Humans , Metformin/adverse effects , Hypoglycemic Agents/adverse effects , Glycated Hemoglobin , Body Weight , Double-Blind Method , Drug Therapy, Combination , Glucose , China , Blood Glucose , Treatment Outcome
15.
BMJ Open ; 14(4): e083550, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38663923

ABSTRACT

OBJECTIVES: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are indicated for the treatment of type 2 diabetes and more recently for weight loss. The aim of this study was to assess the risks associated with GLP1-RA exposure during early pregnancy. DESIGN: This multicentre, observational prospective cohort study compared pregnancy outcomes in women exposed to GLP1-RA in early pregnancy either for diabetes or obesity treatment with those in two reference groups: (1) women with diabetes exposed to at least one non-GLP1-RA antidiabetic drug during the first trimester and (2) a reference group of overweight/obese women without diabetes, between 2009 and 2022. SETTING: Data were collected from the databases of six Teratology Information Services. PARTICIPANTS: This study included 168 pregnancies of women exposed to GLP1-RA during the first trimester, alongside a reference group of 156 pregnancies of women with diabetes and 163 pregnancies of overweight/obese women. RESULTS: Exposure to GLP1-RA in the first trimester was not associated with a risk of major birth defects when compared with diabetes (2.6% vs 2.3%; adjusted OR, 0.98 (95% CI, 0.16 to 5.82)) or to overweight/obese (2.6% vs 3.9%; adjusted OR 0.54 (0.11 to 2.75)). For the GLP1-RA group, cumulative incidence for live births, pregnancy losses and pregnancy terminations was 59%, 23% and 18%, respectively. In the diabetes reference group, corresponding estimates were 69%, 26% and 6%, while in the overweight/obese reference group, they were 63%, 29% and 8%, respectively. Cox proportional cause-specific hazard models indicated no increased risk of pregnancy losses in the GLP1-RA versus the diabetes and the overweight/obese reference groups, in both crude and adjusted analyses. CONCLUSIONS: This study offers reassurance in cases of inadvertent exposure to GLP1-RA during the first trimester of pregnancy. Due to the limited sample size, larger studies are required to validate these findings.


Subject(s)
Glucagon-Like Peptide-1 Receptor , Hypoglycemic Agents , Obesity , Pregnancy Outcome , Pregnancy Trimester, First , Humans , Female , Pregnancy , Prospective Studies , Adult , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Pregnancy Outcome/epidemiology , Obesity/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Abnormalities, Drug-Induced/epidemiology , Pregnancy in Diabetics/drug therapy , Databases, Factual , Pregnancy Complications/drug therapy
16.
BMJ ; 385: e078225, 2024 04 10.
Article in English | MEDLINE | ID: mdl-38683947

ABSTRACT

OBJECTIVE: To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. DESIGN: Scandinavian cohort study. SETTING: Denmark, Norway, and Sweden, 2007-21. PARTICIPANTS: Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. MAIN OUTCOME MEASURES: Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. RESULTS: The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference -0.13, 95% confidence interval -0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05). CONCLUSIONS: In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk.


Subject(s)
Dipeptidyl-Peptidase IV Inhibitors , Glucagon-Like Peptide-1 Receptor , Thyroid Neoplasms , Humans , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/chemically induced , Glucagon-Like Peptide-1 Receptor/agonists , Male , Female , Middle Aged , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Aged , Denmark/epidemiology , Incidence , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Cohort Studies , Adult , Sweden/epidemiology , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Risk Factors , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Norway/epidemiology , Scandinavian and Nordic Countries/epidemiology , Proportional Hazards Models
18.
BMJ Open ; 14(4): e077084, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38626972

ABSTRACT

OBJECTIVE: To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice. DESIGN: A retrospective cohort study. SETTING: Korean Health Insurance Review and Assessment database. PARTICIPANTS: Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018. INTERVENTIONS: Initiation of combination therapy with evogliptin. PRIMARY AND SECONDARY OUTCOME MEASURES: Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs. RESULTS: From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51). CONCLUSIONS: These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population.


Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Heart Failure , Metformin , Myocardial Infarction , Piperazines , Humans , Diabetes Mellitus, Type 2/epidemiology , Cohort Studies , Retrospective Studies , Treatment Outcome , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Sulfonylurea Compounds/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Myocardial Infarction/complications , Heart Failure/epidemiology
19.
Ned Tijdschr Geneeskd ; 1682024 Apr 11.
Article in Dutch | MEDLINE | ID: mdl-38602004

ABSTRACT

Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have gained prominence in the treatment of diabetes mellitus type 2, heart failure, and chronic kidney disease. However, concerns arise for frail older adults, given their underrepresentation in trials and heightened susceptibility to adverse drug events. This review summarizes the clinical effects of SGLT2 inhibitors in older adults with frailty. SGLT2 inhibitors seem to exhibit consistent cardiovascular benefits irrespective of age. As such, these drugs can be beneficial for older adults with 'cardiovascular frailty': in other words, cardiovascular multimorbidity. However, in the current data there is a lack of focus on the broader definition of frailty, which also includes functional status and self-dependence. Also, some research suggest that adverse events, such as volume depletion and genitourinary infections, are more common in the frail older population. Therefore, until more data is available, SGLT2 inhibitors should be prescribed with caution in older adults living with frailty.


Subject(s)
Diabetes Mellitus, Type 2 , Frailty , Sodium-Glucose Transporter 2 Inhibitors , Aged , Humans , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Frail Elderly , Glucose/therapeutic use , Hypoglycemic Agents/adverse effects , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
20.
Medwave ; 24(3): e2758, 2024 Apr 17.
Article in English, Spanish | MEDLINE | ID: mdl-38631041

ABSTRACT

Background: Type 2 diabetes mellitus is a highly prevalent disease and is associated with increased morbidity and mortality. Due to the low percentage of adequate glycemic control, new strategies for the treatment of type 2 diabetes mellitus have been sought, including sodium-glucose cotransporter type 2 inhibitorss. Objective: To describe the evolution of patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital. The primary objective was to evaluate the efficacy of the medication regarding glycosylated hemoglobin A1c (HbA1c). The secondary objectives were: 1) achievement of HbA1c equal to or less than 7.5% according to survival analysis. 2) Change in glomerular filtration rate and urinary albumin excretion post treatment. Methods: Review of clinical records of all patients treated with empagliflozin from November 2019 to June 2023. Average follow-up of 19 (16.3 to 40) months. To compare HbA1c values according to follow-up ranges, the paired T test or Wilcoxon test was used. Results: We included 58 patients, 15 men and 43 women (74.1%), with an average age of 58.5 ± 9.2 years, ranging from 35 to 75 years. Baseline HbA1c of 10.3 ± 1.6% and 8.98% ± 2.2 in a follow-up of 18 to 24 months post-treatment, resulted in a decrease of 1.27% (p = 0.002; confidence interval 95%: 0.5 to 2.03). The most common adverse effect was urinary tract infection. Conclusions: Patients with type 2 diabetes mellitus with insulin requirements treated with empagliflozin at the Peñaflor Hospital achieved better glycemic control with few adverse effects.


Introducción: La diabetes mellitus tipo 2 es una enfermedad de alta prevalencia y está asociada a mayor morbimortalidad. Debido al bajo porcentaje de compensación, se han buscado nuevas estrategias de tratamiento farmacológico, como los inhibidores del cotransportador sodio-glucosa tipo 2. Objetivo: Describir la evolución de pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor, ubicado en el sector poniente de la Región Metropolitana, Chile. El objetivo primario fue evaluar la eficacia del medicamento respecto a hemoglobina glicosilada A1c. Los objetivos secundarios fueron registrar el logro de hemoglobina glicosilada A1c igual o menor a 7,5% según análisis de supervivencia. Luego, consignar el cambio en la velocidad de filtración glomerular y en la excreción urinaria de albúmina post tratamiento. Métodos: Revisión de ficha clínica de todos los pacientes tratados con empagliflozina desde noviembre de 2019 a junio de 2023. Media de seguimiento de 19 (de 16,3 a 40) meses. Para comparación entre valores de hemoglobina glicosilada A1c según rangos de seguimiento, se utilizó prueba T de Student de términos pareados o prueba de Wilcoxon. Resultados: Se estudió a 58 pacientes, 15 hombres y 43 mujeres (74,1%). Edad 58,5 ± 9,2 años, rango de 35 a 75 años. Hemoglobina glicosilada A1c basal de 10,3 ± 1,6% y 8,98% ± 2,2 en un rango de seguimiento de 18 a 24 meses post tratamiento, resultando en un descenso de 1,27% (p = 0,002; intervalo de confianza 95%: 0,5 a 2,03). El efecto adverso más frecuente fue infección del tracto urinario. Conclusiones: Los pacientes diabéticos tipo 2 insulino-requirentes tratados con empagliflozina en el Hospital Peñaflor lograron un mejor control glicémico con pocos efectos adversos.


Subject(s)
Diabetes Mellitus, Type 2 , Glucosides , Insulins , Sodium-Glucose Transporter 2 Inhibitors , Male , Humans , Female , Middle Aged , Aged , Hypoglycemic Agents/adverse effects , Glycated Hemoglobin , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Benzhydryl Compounds/adverse effects , Treatment Outcome , Insulins/therapeutic use , Blood Glucose/metabolism
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