To evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, ...given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug.
After a 4-week run-in to optimize metformin and stop other oral antidiabetic drugs, participants (N = 1,170, mean diabetes duration ∼8.8 years, BMI ∼31.7 kg/m
) were randomly assigned to open-label once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum insulin dose of 60 units/day, or to once-daily Lixi (20 μg/day) while continuing with metformin. The primary outcome was HbA
change at 30 weeks.
Greater reductions in HbA
from baseline (8.1% 65 mmol/mol) were achieved with iGlarLixi compared with iGlar and Lixi (-1.6%, -1.3%, -0.9%, respectively), reaching mean final HbA
levels of 6.5% (48 mmol/mol) for iGlarLixi versus 6.8% (51 mmol/mol) and 7.3% (56 mmol/mol) for iGlar and Lixi, respectively (both P < 0.0001). More subjects reached target HbA
<7% with iGlarLixi (74%) versus iGlar (59%) or Lixi (33%) (P < 0.0001 for all). Mean body weight decreased with iGlarLixi (-0.3 kg) and Lixi (-2.3 kg) and increased with iGlar (+1.1 kg, difference 1.4 kg, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was similar with iGlarLixi and iGlar (1.4 and 1.2 events/patient-year) and lower with Lixi (0.3 events/patient-year). iGlarLixi improved postprandial glycemic control versus iGlar and demonstrated considerably fewer nausea (9.6%) and vomiting (3.2%) events than Lixi (24% and 6.4%, respectively).
iGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA
reductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi.
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as new options in the management of type 2 diabetes mellitus, demonstrating meaningful antihyperglycemic effects and good ...tolerability profiles. Glycemic control is improved by preventing the DPP-4-mediated degradation of incretin hormones, with a resulting increase in insulin secretion and inhibition of glucagon secretion. Purpose: This article provides a discussion of the clinical utility of linagliptin. Results and Conclusion: Linagliptin is a xanthine-based, oral DPP-4 inhibitor that has been approved in the United States and Europe. It has been evaluated extensively in clinical trials, and results in improved glycemic control when used as monotherapy, initial combination therapy with metformin or pioglitazone, add-on therapy to metformin and/or a sulfonylurea, or add-on therapy to basal insulin (with or without oral antidiabetic drugs). Consistent with other members of its class, the benefits of linagliptin also include a low risk of hypoglycemia and weight gain. However, linagliptin is the first DPP-4 inhibitor to be approved as a once-daily, 5-mg dose and, due to its primarily non-renal route of excretion, no dosage adjustment is required for patients with renal or hepatic impairment. The pharmacokinetics and pharmacodynamics of linagliptin are not affected to a clinically meaningful degree by race or ethnicity and linagliptin has very low potential for drug-drug interactions.
Background:
Painful diabetic neuropathy (PDN) is a progressive condition that deprives many patients of quality of life. With limited treatment options available, successful pain management can be ...difficult to achieve.
Methods:
We reviewed results of recent data evaluating high frequency spinal cord stimulation (SCS).
Results
from the SENZA-PDN randomized clinical trial (NCT03228420), the largest such trial to date, demonstrated 10-kHz spinal cord stimulation substantially reduced PDN refractory to conventional medical management along with improvements in health-related quality-of-life measures that were sustained over 12 months. These data supported the recent U.S. Food & Drug Administration (FDA) approval for 10-kHz SCS in PDN patients and contributed to the body of evidence on SCS available to health care professionals managing the effects of PDN.
Conclusion:
High frequency spinal cord simulation appears to hold promise in treatment of painful diabetic neuropathy. We look forward to future works in the literature that will further elucidate these promising findings.
The present short review summarizes and updates clinical experience with two classes of drugs introduced for the management of type 2 diabetes mellitus over the past 8 years: (i) the glucagon‐like ...peptide‐1 receptor agonists; and (ii) the dipeptidyl peptidase 4 inhibitors. Both classes of agents address the so called “incretin defect” in patients with T2DM.
摘要
这篇简短的综述总结与更新了在过去的8年中引进的两类2型糖尿病治疗药物的临床经验： (i)胰高血糖素样肽‐1受体激动剂；以及(ii)二肽基肽酶4抑制剂。这两种类型的药物都是针对T2DM患者的“肠促胰岛素缺陷”。
This trial, which compared once-weekly exenatide plus usual care with usual care alone in patients with type 2 diabetes with or without previous cardiovascular disease, showed no significant ...between-group difference in the rates of major adverse cardiovascular events.
This study assessed the clinical impact of four treatment strategies in adults with type 1 diabetes (T1D): real-time continuous glucose monitoring (rtCGM) with multiple daily insulin injections ...(rtCGM+MDI), rtCGM with continuous subcutaneous insulin infusion (rtCGM+CSII), self-monitoring of blood glucose with MDI (SMBG+MDI), and SMBG with CSII (SMBG+CSII).
This 3-year, nonrandomized, prospective, real-world, clinical trial followed 94 participants with T1D (rtCGM+MDI,
= 22; rtCGM+CSII,
= 26; SMBG+MDI,
= 21; SMBG+CSII,
= 25). The main end points were changes in A1C, time in range (70-180 mg/dL 3.9-10 mmol/L), time below range (<70 mg/dL <3.9 mmol/L), glycemic variability, and incidence of hypoglycemia.
At 3 years, the rtCGM groups (rtCGM+MDI and rtCGM+CSII) had significantly lower A1C (7.0% 53 mmol/mol,
= 0.0002, and 6.9% 52 mmol/mol,
< 0.0001, respectively), compared with the SMBG+CSII and SMBG+MDI groups (7.7% 61 mmol/mol,
= 0.3574, and 8.0% 64 mmol/mol,
= 1.000, respectively), with no significant difference between the rtCGM groups. Significant improvements in percentage of time in range were observed in the rtCGM subgroups (rtCGM+MDI, 48.7-69.0%,
< 0.0001; and rtCGM+CSII, 50.9-72.3%,
< 0.0001) and in the SMBG+CSII group (50.6-57.8%,
= 0.0114). Significant reductions in time below range were found only in the rtCGM subgroups (rtCGM+MDI, 9.4-5.5%,
= 0.0387; and rtCGM+CSII, 9.0-5.3%,
= 0.0235). Seven severe hypoglycemia episodes occurred: SMBG groups,
= 5; sensor-augmented insulin regimen groups,
= 2.
rtCGM was superior to SMBG in reducing A1C, hypoglycemia, and other end points in individuals with T1D regardless of their insulin delivery method. rtCGM+MDI can be considered an equivalent but lower-cost alternative to sensor-augmented insulin pump therapy and superior to treatment with SMBG+MDI or SMBG+CSII therapy.
Sodium-glucose cotransporter (SGLT) inhibitors are new oral antidiabetes medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure, and body weight ...without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment. Several SGLT inhibitors are currently under review by the U.S. Food and Drug Administration and European regulatory agencies as adjuncts to insulin therapy in people with type 1 diabetes. Strategies must be developed and disseminated to the medical community to mitigate the associated DKA risk. This Consensus Report reviews current data regarding SGLT inhibitor use and provides recommendations to enhance the safety of SGLT inhibitors in people with type 1 diabetes.
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