Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic ...polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes.
This phase 3, double-blind, randomised, placebo-controlled trial was conducted in seven countries. Adults (aged ≥18 years) with a body-mass index (BMI) of 27 kg/m2 or higher and glycated haemoglobin (HbA1c) of 7–10% (53–86 mmol/mol) were randomly assigned (1:1:1), using a computer-generated random sequence via a validated interactive web-response system, to receive either once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. All participants, investigators, and the sponsor were masked to treatment assignment. Coprimary endpoints were the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher. The treatment-regimen estimand assessed effects regardless of treatment discontinuation or initiation of antihyperglycaemic rescue therapy. Efficacy and safety endpoints were analysed with data from all randomly assigned participants (intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT04657003.
Between March 29, 2021, and April 10, 2023, of 1514 adults assessed for eligibility, 938 (mean age 54·2 years SD 10·6, 476 51% were female, 710 76% were White, and 561 60% were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315). Baseline mean bodyweight was 100·7 kg (SD 21·1), BMI 36·1 kg/m2 (SD 6·6), and HbA1c 8·02% (SD 0·89; 64·1 mmol/mol SD 9·7). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was –12·8% (SE 0·6) and –14·7% (0·5), respectively, and –3·2% (0·5) with placebo, resulting in estimated treatment differences versus placebo of –9·6% percentage points (95% CI –11·1 to –8·1) with tirzepatide 10 mg and –11·6% percentage points (–13·0 to –10·1) with tirzepatide 15 mg (all p<0·0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79–83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator.
In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in bodyweight, with a safety profile that was similar to other incretin-based therapies for weight management.
Eli Lilly and Company.
Background:
Obstructive sleep apnea (OSA) is associated with metabolic, endocrine, and cardiovascular diseases. It is characterized by repetitive episodes of apnea/hypopnea and hypoxia in tissues, ...which might also impact bone metabolism. This study investigates the possible association between OSA and osteoporosis.
Methods:
Random samples of 1 million individuals were collected from Taiwan's National Health Insurance database. A total of 1377 patients with newly diagnosed OSA from 2000 to 2008 were recruited and compared with a matched cohort of 20 655 patients without OSA. All patients were tracked until an osteoporosis diagnosis, death, or the end of 2011.
Results:
During the 6-year follow-up period, the incidence rates of osteoporosis in the OSA cohort and comparison group were 2.52 and 1.00 per 1000 person-years, respectively. Patients with OSA were found to be at 2.74 times the risk of osteoporosis than patients without OSA (95% confidence interval 1.69–4.44, P < .05), after adjustment for age, gender, diabetes, hypertension, coronary artery disease, obesity, stroke, hyperlipidemia, chronic kidney disease, gout, monthly income, and geographical location. Subgroup analysis showed that older patients and female patients had a higher risk for osteoporosis than their younger and male counterparts. Log-rank analysis revealed that patients with OSA patients had significantly higher cumulative incidence rates of osteoporosis than the comparison group (P < .0001).
Conclusion:
People diagnosed with OSA are at increased risk for subsequent osteoporosis.
Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly ...assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean SD age 59 10 years, 92 men 58%, mean SD baseline HbA
level 8.1% 0.6%) completed the trial. At week 20, HbA
decreased from 8.1% to 7.9% in the TENS group (- 0.2% 95% CI - 0.4% to - 0.1%) and from 8.1% to 7.8% in the placebo group (- 0.3% 95% CI - 0.5% to - 0.2%) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL 95% CI 58, 73 vs. 79 mg/dL 95% CI 72, 87) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA
reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.
Obstructive sleep apnea (OSA) is associated with systemic inflammation and induces various comorbid medical diseases. To date, no study has explored the relationship between OSA and atopic dermatitis ...(AD), an inflammatory and autoimmune skin disorder. This study investigated the longitudinal risk for AD in patients with OSA.
A random sample of 1,000,000 individuals from Taiwan's National Health Insurance database was collected. From this sample, 1222 patients with newly-diagnosed OSA between 2000 and 2005 were identified and compared with a matched cohort of 18330 patients without OSA. All patients were tracked for 5.5 years from the index date in order to identify which patients subsequently developed AD.
During the 5.5-year follow-up period, the incidence rates of AD in the OSA cohort and comparison groups were 9.81 and 6.21 per 1000 person-years, respectively. After adjustment for age, gender, diabetes, hypertension, coronary heart disease, obesity, allergy, allergic rhinitis, asthma, monthly income, and geographic location, patients with OSA were 1.5-times more likely to develop AD than patients without OSA (95% CI = 1.15-1.95, p = 0.0025). The hazard risk for AD was greater in male OSA patients and young OSA patients (0-18 and 19-34 years), adjusted HRs being 1.53 (95% CI = 1.14-2.06, p = 0.005), 4.01(95% CI = 1.57-10.26, p = 0.0038) and 1.75(95% CI = 1.00-3.04, p = 0.0483), respectively. The log-rank test indicated that OSA patients <35-years-old had significantly higher cumulative incidence rates of AD than those patient of the same age in the comparison group (p = 0.0001).
Patients with OSA, especially male patients and younger patients, are at an increased risk for AD later in life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes mellitus (DM) is a known risk factor for dementia. It is unclear whether diabetic ketoacidosis (DKA) further increases the risk of dementia in patients with type 2 DM.
This retrospective ...nationwide population-based cohort study was conducted using Taiwan’s National Health Insurance database. We extracted claims data for 4451 patients with type 2 diabetes and DKA and 8902 diabetic controls matched for age, gender, diabetes complication severity index, frequency of clinic visits and baseline comorbidities between 2000 and 2002. Patients with type 1 diabetes or prior hypoglycemia before index date were excluded. All patients were tracked until new dementia diagnosis, death, or end of 2011.
Of the 4451 DKA patients, 211 (4.7%) and 305 (3.4%) of the 8902 diabetic controls were diagnosed as having dementia during the follow-up period. The incidence rate ratio (IRR) for dementia was 1.62 (95% CI 1.35–1.93; P < 0.0001) for patients with DKA versus diabetic patients without DKA. After adjusting for age, baseline comorbidities, geographic area, and income, patients with DKA were found to have 1.86 times the risk of developing dementia, compared to controls (95% CI 1.56–2.22, P < 0.0001). They were found to have a higher risk of Alzheimer’s dementia (HR:1.86; 95% CI 1.52–2.28, P < 0.0001) but not non-Alzheimer’s dementia.
Type 2 diabetes patients with DKA are at increased risk of Alzheimer’s dementia but not non-Alzheimer dementia.
Background/Purpose The relationship between temperature variability and HbA1c has been reported in Caucasians, but not for Asians of Taiwanese origin. This study investigated the impact of ...temperature on HbA1c in various groups of Taiwanese with type 2 diabetes in Taiwan. Methods For this longitudinal follow-up study which started in 2006, we recruited a total of 4399 patients with type 2 diabetes who had been regularly followed up at Chi Mei Medical Center and obtained local temperature data for 2006 to 2011 from Taiwan's Central Weather Bureau. We used a generalized estimated equation (GEE) to analyze the HbA1c level and its change over time with temperature and temperature changes, respectively. Results We found a negative correlation between HbA1c and temperature ( R = −0.475, p = 0.001). For every 1°C decrement in temperature, there was an increase in the risk of having a HbA1c level >7% p < 0.001, adjusted odds ratio (OR): 1.01. There was a significantly higher risk of HbA1c > 7% among those in the lowest quartile of temperatures than the highest quartile ( p = 0.0038, adjusted OR: 1.13). Patients with diabetic patients were at higher risk of HbA1C > 7% in the winter and spring than those in the summer (adjusted OR: 1.13, p = 0.0027; adjusted OR: 1.14, p = 0.0022). After adjusting for various confounders, we found people who were younger than 65 years old, people who had diabetes for longer than 6 years, and people who had a body mass index (BMI) < 24 to be more susceptible to temperature changes ( p = 0.0022, β: 0.0095; p < 0.0001, β: 0.0125; p < 0.0001, β: 0.016, respectively). Conclusion Our study suggests cold weather may adversely affect HbA1c levels in Taiwanese people with type 2 diabetes, especially in people under 65 years old, people with diabetes for longer than 6 years, and those with a BMI < 24.
To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan.
In this multicenter retrospective study, adult ...patients with T2DM who initiated dapagliflozin after May 1
2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression.
A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval CI -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (
= 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c.
In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.
Abstract Aim To compare the efficacy and safety of acarbose plus metformin fixed-dose combination (FDC) versus acarbose monotherapy for type 2 diabetes (T2D). Methods Eligible T2D patients undergoing ...treatment with diet control only or oral antidiabetic medications were run-in on acarbose 50 mg thrice-daily for 4 weeks, then randomised either to continue this monotherapy, or to acarbose 50 mg plus metformin hydrochloride 500 mg FDC (acarbose/metformin FDC), each thrice-daily for 16 weeks. Results Acarbose/metformin FDC therapy significantly reduced HbA1c, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) from baseline (all p < 0.0001) with superior efficacy compared with acarbose monotherapy (between-group differences; HbA1c −1.35%; FPG −29.5 mg/dl; PPG −41.6 mg/dl; all p < 0.0001). Proportionally more patients treated with acarbose/metformin FDC achieved HbA1c <7.0% (47.8% vs. 10.7%, p < 0.0001). Both treatments reduced bodyweight ( p < 0.0001), with a significant between-group difference (−0.6 kg, p < 0.01) favouring acarbose/metformin FDC. Hypoglycaemia was not reported with either treatment, and the incidence of other adverse events did not differ significantly between the groups. Conclusions Compared with acarbose monotherapy, acarbose/metformin FDC has superior antihyperglycaemic efficacy, brings proportionally more T2D patients to HbA1c goal, and further reduces bodyweight. Acarbose/metformin FDC is well-tolerated without significant risk of hypoglycaemia and is a potentially advantageous therapy for T2D.
Context:
Previous studies have reported an increased prevalence of sudden sensorineural hearing loss (SSNHL) in osteoporotic patients. However, the risk of SSNHL in this population remains unclear.
...Objective:
This study investigated the risk of SSNHL in osteoporotic patients.
Setting:
Taiwan launched a single-payer National Health Insurance (NHI) program on March 1, 1995. NHI covers nearly all of Taiwan's residents.
Design:
Using randomized representative sample of one million individuals from Taiwan's National Health Insurance claims database, we compared the data of 10 660 patients with newly diagnosed osteoporosis from 1998–2008 and with 31 980 patients without osteoporosis. All patients were tracked until SSNHL was diagnosed, death, or the end of 2011. Osteoporosis was identified based on a primary diagnosis of osteoporosis (ICD-9-CM code 7330) by dual-energy x-ray absorptiometry.
Intervention:
Identified the diagnosis of osteoporosis and SSNHL by ICD-9CM code.
Main Outcome Measure:
The identification of patients with newly diagnosed SSNHL by ICD-9CM code.
Results:
The incidence rates of SSNHL in the osteoporosis cohort and comparison group were 10.43 and 5.93 per 10 000 person years. Patients with osteoporosis were at 1.76 times the risk of developing SSNHL than patients without osteoporosis. The incidence rate ratio (IRR) for SSNHL was significantly greater in older (50–64 y and ≥65 y), and female patients, and borderline greater in hypertensive patients with osteoporosis than the controls, IRRs being 1.50, 2.33, 1.87, and 1.59.
Conclusions:
Patients with osteoporosis are at significantly greater risk of developing SSNHL.
PDF
