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Saudi Medical Journal Apr 2015Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. It is associated with maternal and neonatal adverse outcomes. Maintaining... (Review)
Review
Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. It is associated with maternal and neonatal adverse outcomes. Maintaining adequate blood glucose levels in GDM reduces morbidity for both mother and baby. There is a lack of uniform strategies for screening and diagnosing GDM globally. This review covers the latest update in the diagnosis and management of GDM. The initial treatment of GDM consists of diet and exercise. If these measures fail to achieve glycemic goals, insulin should be initiated. Insulin analogs are more physiological than human insulin, and are associated with less risk of hypoglycemia, and may provide better glycemic control. Insulin lispro, aspart, and detemir are approved to be used in pregnancy. Insulin glargine is not approved in pregnancy, but the existing studies did not show any contraindications. The use of oral hypoglycemic agents; glyburide and metformin seems to be safe and effective in pregnancy.
Topics: Diabetes, Gestational; Diet; Exercise Therapy; Female; Humans; Hypoglycemic Agents; Pregnancy; Risk Factors
PubMed: 25828275
DOI: 10.15537/smj.2015.4.10307 -
JAMA Nov 2023Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Tirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described.
OBJECTIVE
To assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine.
DESIGN, SETTING, AND PARTICIPANTS
This open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin.
INTERVENTIONS
Participants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).
MAIN OUTCOMES AND MEASURES
Outcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%.
RESULTS
Among 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was -2.1% vs -1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, -0.98% [95% CI, -1.17% to -0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was -9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, -12.2 kg [95% CI, -13.4 to -10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro.
CONCLUSIONS AND RELEVANCE
In people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04537923.
Topics: Female; Humans; Male; Middle Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Treatment Outcome; Internationality; Aged
PubMed: 37786396
DOI: 10.1001/jama.2023.20294 -
The Cochrane Database of Systematic... Jan 2016Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diabetic ketoacidosis (DKA) is an acute, life-threatening complication of uncontrolled diabetes that mainly occurs in individuals with autoimmune type 1 diabetes, but it is not uncommon in some people with type 2 diabetes. The treatment of DKA is traditionally accomplished by the administration of intravenous infusion of regular insulin that is initiated in the emergency department and continued in an intensive care unit or a high-dependency unit environment. It is unclear whether people with DKA should be treated with other treatment modalities such as subcutaneous rapid-acting insulin analogues.
OBJECTIVES
To assess the effects of subcutaneous rapid-acting insulin analogues for the treatment of diabetic ketoacidosis.
SEARCH METHODS
We identified eligible trials by searching MEDLINE, PubMed, EMBASE, LILACS, CINAHL, and the Cochrane Library. We searched the trials registers WHO ICTRP Search Portal and ClinicalTrials.gov. The date of last search for all databases was 27 October 2015. We also examined reference lists of included randomised controlled trials (RCTs) and systematic reviews, and contacted trial authors.
SELECTION CRITERIA
We included trials if they were RCTs comparing subcutaneous rapid-acting insulin analogues versus standard intravenous infusion in participants with DKA of any age or sex with type 1 or type 2 diabetes, and in pregnant women.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data, assessed studies for risk of bias, and evaluated overall study quality utilising the GRADE instrument. We assessed the statistical heterogeneity of included studies by visually inspecting forest plots and quantifying the diversity using the I² statistic. We synthesised data using random-effects model meta-analysis or descriptive analysis, as appropriate.
MAIN RESULTS
Five trials randomised 201 participants (110 participants to subcutaneous rapid-acting insulin analogues and 91 to intravenous regular insulin). The criteria for DKA were consistent with the American Diabetes Association criteria for mild or moderate DKA. The underlying cause of DKA was mostly poor compliance with diabetes therapy. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Four trials evaluated the effects of the rapid-acting insulin analogue lispro, and one the effects of the rapid-acting insulin analogue aspart. The mean follow-up period as measured by mean hospital stay ranged between two and seven days. Overall, risk of bias of the evaluated trials was unclear in many domains and high for performance bias for the outcome measure time to resolution of DKA.No deaths were reported in the included trials (186 participants; 3 trials; moderate- (insulin lispro) to low-quality evidence (insulin aspart)). There was very low-quality evidence to evaluate the effects of subcutaneous insulin lispro versus intravenous regular insulin on the time to resolution of DKA: mean difference (MD) 0.2 h (95% CI -1.7 to 2.1); P = 0.81; 90 participants; 2 trials. In one trial involving children with DKA, the time to reach a glucose level of 250 mg/dL was similar between insulin lispro and intravenous regular insulin. There was very low-quality evidence to evaluate the effects of subcutaneous insulin aspart versus intravenous regular insulin on the time to resolution of DKA: MD -1 h (95% CI -3.2 to 1.2); P = 0.36; 30 participants; 1 trial. There was low-quality evidence to evaluate the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin on hypoglycaemic episodes: 6 of 80 insulin lispro-treated participants compared with 9 of 76 regular insulin-treated participants reported hypoglycaemic events; risk ratio (RR) 0.59 (95% CI 0.23 to 1.52); P = 0.28; 156 participants; 4 trials. For insulin aspart compared with regular insulin, RR for hypoglycaemic episodes was 1.00 (95% CI 0.07 to 14.55); P = 1.0; 30 participants; 1 trial; low-quality evidence. Socioeconomic effects as measured by length of mean hospital stay for insulin lispro compared with regular insulin showed a MD of -0.4 days (95% CI -1 to 0.2); P = 0.22; 90 participants; 2 trials; low-quality evidence and for insulin aspart compared with regular insulin 1.1 days (95% CI -3.3 to 1.1); P = 0.32; low-quality evidence. Data on morbidity were limited, but no specific events were reported for the comparison of insulin lispro with regular insulin. No trial reported on adverse events other than hypoglycaemic episodes, and no trial investigated patient satisfaction.
AUTHORS' CONCLUSIONS
Our review, which provided mainly data on adults, suggests on the basis of mostly low- to very low-quality evidence that there are neither advantages nor disadvantages when comparing the effects of subcutaneous rapid-acting insulin analogues versus intravenous regular insulin for treating mild or moderate DKA.
Topics: Adult; Child; Diabetic Ketoacidosis; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Aspart; Insulin Lispro; Insulin, Short-Acting; Randomized Controlled Trials as Topic; Young Adult
PubMed: 26798030
DOI: 10.1002/14651858.CD011281.pub2 -
Journal of Clinical and Experimental... 2022The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar... (Review)
Review
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
PubMed: 35535116
DOI: 10.1016/j.jceh.2021.09.010 -
The New England Journal of Medicine Sep 2022Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.
METHODS
In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.
RESULTS
A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group.
CONCLUSIONS
In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).
Topics: Adolescent; Adult; Aged; Bionics; Blood Glucose; Blood Glucose Self-Monitoring; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Middle Aged; Young Adult
PubMed: 36170500
DOI: 10.1056/NEJMoa2205225 -
Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews.The Cochrane Database of Systematic... Aug 2018Successful treatments for gestational diabetes mellitus (GDM) have the potential to improve health outcomes for women with GDM and their babies. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Successful treatments for gestational diabetes mellitus (GDM) have the potential to improve health outcomes for women with GDM and their babies.
OBJECTIVES
To provide a comprehensive synthesis of evidence from Cochrane systematic reviews of the benefits and harms associated with interventions for treating GDM on women and their babies.
METHODS
We searched the Cochrane Database of Systematic Reviews (5 January 2018) for reviews of treatment/management for women with GDM. Reviews of pregnant women with pre-existing diabetes were excluded.Two overview authors independently assessed reviews for inclusion, quality (AMSTAR; ROBIS), quality of evidence (GRADE), and extracted data.
MAIN RESULTS
We included 14 reviews. Of these, 10 provided relevant high-quality and low-risk of bias data (AMSTAR and ROBIS) from 128 randomised controlled trials (RCTs), 27 comparisons, 17,984 women, 16,305 babies, and 1441 children. Evidence ranged from high- to very low-quality (GRADE). Only one effective intervention was found for treating women with GDM.EffectiveLifestyle versus usual careLifestyle intervention versus usual care probably reduces large-for-gestational age (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.50 to 0.71; 6 RCTs, N = 2994; GRADE moderate-quality).PromisingNo evidence for any outcome for any comparison could be classified to this category.Ineffective or possibly harmful Lifestyle versus usual careLifestyle intervention versus usual care probably increases the risk of induction of labour (IOL) suggesting possible harm (average RR 1.20, 95% CI 0.99 to 1.46; 4 RCTs, N = 2699; GRADE moderate-quality).Exercise versus controlExercise intervention versus control for return to pre-pregnancy weight suggested ineffectiveness (body mass index, BMI) MD 0.11 kg/m², 95% CI -1.04 to 1.26; 3 RCTs, N = 254; GRADE moderate-quality).Insulin versus oral therapyInsulin intervention versus oral therapy probably increases the risk of IOL suggesting possible harm (RR 1.3, 95% CI 0.96 to 1.75; 3 RCTs, N = 348; GRADE moderate-quality).Probably ineffective or harmful interventionsInsulin versus oral therapyFor insulin compared to oral therapy there is probably an increased risk of the hypertensive disorders of pregnancy (RR 1.89, 95% CI 1.14 to 3.12; 4 RCTs, N = 1214; GRADE moderate-quality).InconclusiveLifestyle versus usual careThe evidence for childhood adiposity kg/m² (RR 0.91, 95% CI 0.75 to 1.11; 3 RCTs, N = 767; GRADE moderate-quality) and hypoglycaemia was inconclusive (average RR 0.99, 95% CI 0.65 to 1.52; 6 RCTs, N = 3000; GRADE moderate-quality).Exercise versus controlThe evidence for caesarean section (RR 0.86, 95% CI 0.63 to 1.16; 5 RCTs, N = 316; GRADE moderate quality) and perinatal death or serious morbidity composite was inconclusive (RR 0.56, 95% CI 0.12 to 2.61; 2 RCTs, N = 169; GRADE moderate-quality).Insulin versus oral therapyThe evidence for the following outcomes was inconclusive: pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 RCTs, N = 2060), caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 RCTs, N = 1988), large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 RCTs, N = 2352), and perinatal death or serious morbidity composite (RR 1.03; 95% CI 0.84 to 1.26; 2 RCTs, N = 760). GRADE assessment was moderate-quality for these outcomes.Insulin versus dietThe evidence for perinatal mortality was inconclusive (RR 0.74, 95% CI 0.41 to 1.33; 4 RCTs, N = 1137; GRADE moderate-quality).Insulin versus insulinThe evidence for insulin aspart versus lispro for risk of caesarean section was inconclusive (RR 1.00, 95% CI 0.91 to 1.09; 3 RCTs, N = 410; GRADE moderate quality).No conclusions possibleNo conclusions were possible for: lifestyle versus usual care (perineal trauma, postnatal depression, neonatal adiposity, number of antenatal visits/admissions); diet versus control (pre-eclampsia, caesarean section); myo-inositol versus placebo (hypoglycaemia); metformin versus glibenclamide (hypertensive disorders of pregnancy, pregnancy-induced hypertension, death or serious morbidity composite, insulin versus oral therapy (development of type 2 diabetes); intensive management versus routine care (IOL, large-for-gestational age); post- versus pre-prandial glucose monitoring (large-for-gestational age). The evidence ranged from moderate-, low- and very low-quality.
AUTHORS' CONCLUSIONS
Currently there is insufficient high-quality evidence about the effects on health outcomes of relevance for women with GDM and their babies for many of the comparisons in this overview comparing treatment interventions for women with GDM. Lifestyle changes (including as a minimum healthy eating, physical activity and self-monitoring of blood sugar levels) was the only intervention that showed possible health improvements for women and their babies. Lifestyle interventions may result in fewer babies being large. Conversely, in terms of harms, lifestyle interventions may also increase the number of inductions. Taking insulin was also associated with an increase in hypertensive disorders, when compared to oral therapy. There was very limited information on long-term health and health services costs. Further high-quality research is needed.
Topics: Diabetes, Gestational; Exercise; Female; Humans; Hypertension; Hypoglycemic Agents; Infant, Newborn; Insulin; Labor, Induced; Life Style; Pregnancy; Pregnancy Complications, Cardiovascular; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 30103263
DOI: 10.1002/14651858.CD012327.pub2 -
Indian Journal of Endocrinology and... 2015Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and...
Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use.
PubMed: 26425485
DOI: 10.4103/2230-8210.163214 -
Revue Medicale de Liege Jan 2021Development of new insulins aims to mimic in a better way the natural physiology of this hormone secreted by the pancreas. Rapid insulin analogues have proven a better... (Review)
Review
Development of new insulins aims to mimic in a better way the natural physiology of this hormone secreted by the pancreas. Rapid insulin analogues have proven a better capacity to reduce postprandial glycaemic peaks after eating. Nevertheless, these molecules are still quite inaccurate to limit glycaemic excursions after the meals. This reality is often described by patients using continuous glucose monitoring systems. So, there is undeniably a place for even more rapid insulins. The ones named «ultra-rapid insulin» tend to better control hyperglycaemia after meals thanks to more favourable profiles regarding pharmacodynamics and pharmacokinetics. Ultra-rapid lispro (URLi) Lyumjev®, is the new ultra-rapid insulin available in Belgium. This review aims to describe its advantages compared to some other rapid insulins thanks to data obtained from trials in type 1 and type 2 diabetes.
Topics: Belgium; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Insulin Lispro
PubMed: 33443332
DOI: No ID Found