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.
OBJECTIVE
To examine the safety and efficacy of dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, added on to pioglitazone in type 2 diabetes inadequately controlled on pioglitazone.
...RESEARCH DESIGN AND METHODS
Treatment-naive patients or those receiving metformin, sulfonylurea, or thiazolidinedione entered a 10-week pioglitazone dose-optimization period with only pioglitazone. They were then randomized, along with patients previously receiving pioglitazone ≥30 mg, to 48 weeks of double-blind dapagliflozin 5 (n = 141) or 10 mg (n = 140) or placebo (n = 139) every day plus open-label pioglitazone. The primary objective compared HbA1c change from baseline with dapagliflozin plus pioglitazone versus placebo plus pioglitazone at week 24. Primary analysis was based on ANCOVA model using last observation carried forward; all remaining analyses used repeated-measures analysis.
RESULTS
At week 24, the mean reduction from baseline in HbA1c was −0.42% for placebo versus −0.82 and −0.97% for dapagliflozin 5 and 10 mg groups, respectively (P = 0.0007 and P < 0.0001 versus placebo). Patients receiving pioglitazone alone had greater weight gain (3 kg) than those receiving dapagliflozin plus pioglitazone (0.7–1.4 kg) at week 48. Through 48 weeks: hypoglycemia was rare; more events suggestive of genital infection were reported with dapagliflozin (8.6–9.2%) than placebo (2.9%); events suggestive of urinary tract infection showed no clear drug effect (5.0–8.5% for dapagliflozin and 7.9% for placebo); dapagliflozin plus pioglitazone groups had less edema (2.1–4.3%) compared with placebo plus pioglitazone (6.5%); and congestive heart failure and fractures were rare.
CONCLUSIONS
In patients with type 2 diabetes inadequately controlled on pioglitazone, the addition of dapagliflozin further reduced HbA1c levels and mitigated the pioglitazone-related weight gain without increasing hypoglycemia risk.
Resumen Objetivos Calcular la prevalencia de obesidad y sobrepeso en niños y adolescentes de nuestra ciudad e investigar los factores asociados. Sujetos y métodos Estudio transversal de 1.317 niños y ...adolescentes de 2 a 16 años. Mediante muestreo probabilístico polietápico se seleccionaron 3 grupos: 411 de 12 a 16, 504 de 6 a 12 y 402 de 2 a 6 años. Se les calculó el índice de masa corporal y se definió obesidad y sobrepeso según la International Obesity Task Force. Se realizó un cuestionario de consumo de alimentos y de características clínicas y sociodemográficas. Los resultados se expresan como porcentajes (intervalos de confianza al 95%). Mediante regresión logística múltiple se estudió la asociación entre exceso de peso (obesidad y sobrepeso) y las distintas variables, calculando la odds ratio (OR) ajustada. Resultados El 9,5% (8,0-11,0) de los niños y adolescentes de 2 a 16 años son obesos y 22,4% (23,3-24,6) tienen sobrepeso. En el grupo de 12 a 16 años, el 8,5% (5,9-11,2) son obesos y el 20,5% (16,7-24,3) tienen sobrepeso, en el grupo de 6 a 12 años el 11,6% (8,9-14,3) y el 31,0% (27,0-35,0) y en el de 2 a 6 años el 8,0% (5,4-10,6) y el 13,6% (10,3-16,9), respectivamente. Se asocian con el exceso de peso la edad (OR 1,21; p < 0,001), la obesidad materna (OR 10,99; p = 0,008), el peso al nacer mayor de 4 kg (OR 2,91; p = 0,002) y la lactancia artificial exclusiva (OR 1,82; p = 0,005). Conclusión La obesidad y el sobrepeso infantil y juvenil son problemas extraordinariamente prevalentes en nuestra ciudad.
An association between arterial blood pressure and blood viscosity has been suggested in healthy and in diabetic subjects, and that the hemorheological pattern may be influenced by blood lipid ...alterations. In diabetic patients a relationship between arterial hypertension and blood lipid changes may therefore be suggested. This study concerns 19 type II diabetics with hyperlipidemia (triglycerides = 3.2 +/- 1 mmol/l; total cholesterol = 6.1 +/- 1.2 mmol/l; HDL-cholesterol = 0.92 +/- 0.27 mmol/l; VLDL = 29 +/- 5%) (group A), and 19 normolipidemic type II diabetics (triglycerides = 1.15 +/- 0.5 mmol/l; total cholesterol = 5.1 +/- 1 mmol/l; HDL-cholesterol = 1.25 +/- 0.38 mmol/l; VLDL = 20 +/- 5%) (group B). No differences concerning age, body weight, duration of diabetes and glycemic control were found in hyperlipidemic compared to normolipidemic diabetics. On the contrary, higher systolic and diastolic blood pressure levels were demonstrated in group A (167 +/- 14 mmHg and 101 +/- 5.2 mmHg, respectively) than in group B (144 +/- 15 mmHg, p less than 0.001 and 87 +/- 6.9 mmHg, p less than 0.001, respectively). An increase of plasma apolipoprotein B level (163 +/- 27 mg/dl vs 102 +/- 21 mg/dl, p less than 0.001), of plasma viscosity (1.81 +/- 0.08 mPas vs 1.51 +/- 0.07 mPas, p less than 0.001) and of blood viscosity (5.37 +/- 0.33 mPas vs 5.07 +/- 0.04 mPas, p less than 0.01, at shear-rate of 90 s-1; 18.4 +/- 1 mPas vs 14.1 +/- 0.9 mPas, p less than 0.001 at shear-rate of 2.25 s-1) was found in group A, compared to group B.
PDF
