Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis

Efficacy and safety of short- and long-acting GLP-1 receptor agonists on a background of basal insulin in type 2 diabetes: A meta-analysis

10.2337/figshare.12272840.v1 ◽

2020 ◽

Author(s):

Jessica Annalena Huthmacher ◽

Juris J. Meier ◽

Michael A. Nauck

Keyword(s):

Body Weight ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Basal Insulin ◽

Meta Analysis ◽

Efficacy And Safety ◽

Short Acting ◽

Fasting Plasma ◽

Long Acting

Background/Purpose. To compare efficacy and safety of short- and long-acting GLP-1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin in patients with type 2 diabetes. Data Sources/Study Selection. Randomized controlled trials comparing the co-administration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs. Data Extraction/Data Synthesis. Differences in HbA1c, fasting plasma glucose, body weight and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis. Limitations. Relatively small numbers of available publications, some heterogeneity regarding protocols and differences in the GLP-1 RA compound used. Conclusions. Long-acting GLP-1 RAs more effectively reduced HbA1c (∆ - 6 mmol/mol, [95 % CI - 10; - 2], p= 0.007), fasting plasma glucose (∆ - 0.7 mmol/l [- 1.2; - 0.3] p= 0.007) and body weight (∆ - 1.4 kg [- 2.2; - 0.6] p= 0.002) and raised the proportion of patients achieving an HbA1c target < 7.0% (< 53 mmol/mol; p= 0.03) more than the short-acting ones. Patients reporting symptomatic (p= 0.048), but not severe hypoglycemia (p= 0.96) were fewer with long- vs. short-acting GLP-1 RAs added to insulin. The proportion of patients reporting nausea (- 52 %; p < 0.0001) or vomiting (- 36 %; p= 0.0002) was lower with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA1c, fasting plasma glucose and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastro-intestinal tolerability.

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Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis

10.2337/figshare.12272840.v2 ◽

2020 ◽

Author(s):

Jessica Annalena Huthmacher ◽

Juris J. Meier ◽

Michael A. Nauck

Keyword(s):

Body Weight ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Basal Insulin ◽

Meta Analysis ◽

Efficacy And Safety ◽

Short Acting ◽

Fasting Plasma ◽

Long Acting

Background/Purpose. To compare efficacy and safety of short- and long-acting GLP-1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin in patients with type 2 diabetes. Data Sources/Study Selection. Randomized controlled trials comparing the co-administration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs. Data Extraction/Data Synthesis. Differences in HbA1c, fasting plasma glucose, body weight and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis. Limitations. Relatively small numbers of available publications, some heterogeneity regarding protocols and differences in the GLP-1 RA compound used. Conclusions. Long-acting GLP-1 RAs more effectively reduced HbA1c (∆ - 6 mmol/mol, [95 % CI - 10; - 2], p= 0.007), fasting plasma glucose (∆ - 0.7 mmol/l [- 1.2; - 0.3] p= 0.007) and body weight (∆ - 1.4 kg [- 2.2; - 0.6] p= 0.002) and raised the proportion of patients achieving an HbA1c target < 7.0% (< 53 mmol/mol; p= 0.03) more than the short-acting ones. Patients reporting symptomatic (p= 0.048), but not severe hypoglycemia (p= 0.96) were fewer with long- vs. short-acting GLP-1 RAs added to insulin. The proportion of patients reporting nausea (- 52 %; p < 0.0001) or vomiting (- 36 %; p= 0.0002) was lower with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA1c, fasting plasma glucose and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastro-intestinal tolerability.

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Soliqua (Lixi Lan): Sustained Long Term Cost Efficacy and Safety When Used in Combination with Metformin and Glimepiride

Journal of Advances in Medical and Pharmaceutical Sciences ◽

10.9734/jamps/2021/v23i1030263 ◽

2021 ◽

pp. 15-21

Author(s):

Udaya M. Kabadi ◽

Sarah Exley

Keyword(s):

Type 2 Diabetes ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Basal Insulin ◽

Efficacy And Safety ◽

Fasting Plasma ◽

Daily Dose ◽

Hba1c Levels

Background: Previous studies using basal insulin documented the lowest daily dose and least hypoglycemic events when combined with Glimepiride and Metformin while attaining desirable glycemic control. However, Pivotal trials with Soliqua excluded Glimepiride as a part of therapy as well as subjects with moderate obesity (BMI > 35kg/m2). Moreover, these trials were relatively short term. Objective: Assess long term efficacy and safety of Soliqua in combination with Glimepiride and Metformin in subjects with type 2 diabetes irrespective of BMI in ‘real world’ experience. Subjects: 30 adults with type 2 diabetes, age range 32-72 years with HbA1C >7.5% while receiving therapy with 1) Glimepiride, Metformin and Basal insulin and 2) Metformin and/or DPP 4 inhibitors and/or other SUs and /or GLP1 RA and/or Basal insulin and/or prandial insulin. Type 2 diabetes was confirmed by presence of C-peptide. Subjects with history of gastroparesis, Triglycerides over 300 mg/dl and pancreatitis were excluded. Subjects with elevated liver enzymes, over 2.5 times normal and EGFR < 30 ml/min were excluded as well. Methods: All prior therapies were discontinued. All subjects were started on Glimepiride 8 mg, Metformin 1000-2000 mg and SC Soliqua was initiated prior to breakfast with daily dose 15 or 30 units as recommended. Daily dose was increased by 2 units every 3 days until AM fasting plasma glucose of 80-130 mg/dl was attained or the dose of 60 units was reached. The stable daily dose of Soliqua was continued until the time of analysis. Comparisons were conducted between body weights (kg), fasting plasma glucose (FPG) and HbA1C prior to initiation of combination therapy (pre Rx) and every 3-6 months until the time of analysis (post Rx). Results: BMI ranged between 22-67 kg/m2. Duration of diabetes was 5-25 years. Duration of therapy with the combination therapy range, 7-56 months. Subjects were divided into 2 groups according to desirable HbA1C levels as per recommendations by ADA: 1) desirable HbA1C is < 7.0%, 2) desirable HbA1C 7-8 %. Both Fasting plasma glucose (mg/dl) and HbA1C (%) declined from 167 ± 10 and 9.7 ± 0.8 to 114 ± 4 and 7.6± 0.3 at the time of analyses (post Rx) respectively in the whole cohort. In 4 (0.13 %) morbidly obese subjects, FPG and HbA1C levels declined though not achieving desirable glycemic goals despite receiving maximal daily dose, 60 units of Soliqua. All four belonged to group 1. In the remaining 17 subjects desirable glycemic levels were attained and maintained. In group 2, desirable glycemia was reached in all 9 subjects. Symptomatic hypoglycemic events confirmed by blood sugar <70 mg/dl were reported by 4 subjects, none requiring secondary assistance. No severe hypoglycemia was reported. Mean daily dose of Soliqua was lower when compared to the pivotal trials. Conclusion: Soliqua is effective and safe in the long term in all subjects irrespective of BMI when administered in combination with Glimepiride and Metformin. Moreover, lesser daily dose required to attain desirable glycemia with this oral combination may render it to be effective without attaining maximum daily dose in subjects with higher BMIs documented in pivotal trials using Metformin alone.

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Fasting plasma glucose variability levels and risk of adverse outcomes among patients with type 2 diabetes: A systematic review and meta-analysis

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2018.12.010 ◽

2019 ◽

Vol 148 ◽

pp. 23-31 ◽

Cited By ~ 8

Author(s):

Qian Zhao ◽

Fan Zhou ◽

Yusheng Zhang ◽

Xiaoyan Zhou ◽

Changjiang Ying

Keyword(s):

Systematic Review ◽

Type 2 Diabetes ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Meta Analysis ◽

Glucose Variability ◽

Adverse Outcomes ◽

Fasting Plasma

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Randomized, Double-Blinded, Double-Dummy, Active-Controlled, and Multiple-Dose Clinical Study Comparing the Efficacy and Safety of Mulberry Twig (Ramulus Mori, Sangzhi) Alkaloid Tablet and Acarbose in Individuals with Type 2 Diabetes Mellitus

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/7121356 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Mengyi Li ◽

Xuemin Huang ◽

Hui Ye ◽

Yao Chen ◽

Jing Yu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Efficacy And Safety ◽

Postprandial Plasma Glucose ◽

Glucose Levels ◽

Fasting Plasma ◽

Significant Difference

Aims. To evaluate the efficacy and safety of mulberry twig alkaloid (SZ-A) tablet compared with acarbose in patients with type 2 diabetes.Methods. This clinical trial enrolled 38 patients who were randomized into two groups (SZ-A: 23; acarbose: 15) and were treated for 24 weeks. Patients and clinical trial staffs were masked to treatment assignment throughout the study. The primary outcome measures were glycated hemoglobin (HbA1c) and 1-hour and 2-hour postprandial and fasting plasma glucose levels from baseline to the end of treatment. Analysis included all patients who completed this study.Results. By the end of this study, HbA1c level in SZ-A group was decreased from baseline significantly (P<0.001). No significant difference was found when compared with acarbose group (P=0.652). Similarly, 1-hour and 2-hour postprandial plasma glucose levels in SZ-A group were decreased from baseline statistically (P<0.05), without any significant differences compared with acarbose group (P=0.748and 0.558, resp.). The fasting plasma glucose levels were not significantly changed in both groups. One of 23 patients in SZ-A group (4.76%) and 5 of 15 patients in acarbose group (33.33%) suffered from gastrointestinal adverse events.Conclusions. Compared with acarbose, SZ-A tablet was effective and safe in glycemic control in patients with type 2 diabetes.

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Guesstimate Probable Partial Recovery of Pancreatic Beta Cells Using Calculations of Annualized Fasting Plasma Glucose Decreased Amount (GH-Method: mathphysical medicine)

Medical & Clinical Research ◽

10.33140/mcr.05.05.01 ◽

2020 ◽

Vol 5 (5) ◽

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Beta Cells ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Pancreatic Beta Cells ◽

Partial Recovery ◽

Fasting Plasma ◽

Regeneration Capability

In this paper, the author describes his hypothesis on the probable partial self-recovery of some insulin regeneration capability of pancreatic beta cells on a type 2 diabetes (T2D) patient via his collected data of fasting plasma glucose (FPG) and body weight during the period of 1/1/2014 to 11/2/2019.

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Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta‐analysis of seven phase III trials

Diabetes Obesity and Metabolism ◽

10.1111/dom.12623 ◽

2016 ◽

Vol 18 (7) ◽

pp. 721-724 ◽

Cited By ~ 4

Author(s):

J. Seufert ◽

T. Bailey ◽

S. Barkholt Christensen ◽

M. A. Nauck

Keyword(s):

Body Weight ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Meta Analysis ◽

Glycated Haemoglobin ◽

Diabetes Duration ◽

Phase Iii ◽

Fasting Plasma ◽

Phase Iii Trials

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Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis

Diabetes Care ◽

10.2337/dc20-0498 ◽

2020 ◽

Vol 43 (9) ◽

pp. 2303-2312 ◽

Cited By ~ 1

Author(s):

Jessica A. Huthmacher ◽

Juris J. Meier ◽

Michael A. Nauck

Keyword(s):

Type 2 Diabetes ◽

Basal Insulin ◽

Meta Analysis ◽

Efficacy And Safety ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Long Acting

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Guesstimate Probable Partial Recovery of Pancreatic Beta Cells Using Calculations of Annualized Fasting Plasma Glucose Decreased Amount (GH-Method: mathphysical medicine)

Medical & Clinical Research ◽

10.33140/mcr.05.05.001 ◽

2020 ◽

Vol 5 (5) ◽

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Beta Cells ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Pancreatic Beta Cells ◽

Partial Recovery ◽

Fasting Plasma ◽

Regeneration Capability

In this paper, the author describes his hypothesis on the probable partial self-recovery of some insulin regeneration capability of pancreatic beta cells on a type 2 diabetes (T2D) patient via his collected data of fasting plasma glucose (FPG) and body weight during the period of 1/1/2014 to 11/2/2019.

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Efficacy and safety of patient-led versus physician-led titration of basal insulin in patients with uncontrolled type 2 diabetes: a meta-analysis of randomized controlled trials

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001477 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001477

Author(s):

Marco Castellana ◽

Filippo Procino ◽

Rodolfo Sardone ◽

Pierpaolo Trimboli ◽

Gianluigi Giannelli

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Basal Insulin ◽

Meta Analysis ◽

Insulin Dose ◽

Efficacy And Safety ◽

Randomized Controlled ◽

Medication Discontinuation ◽

Patient Reported

IntroductionInsulin is the most effective antihyperglycemic treatment and basal insulin is the preferred initial formulation in patients with type 2 diabetes. However, its effects are dose-dependent, so adequate titration is necessary to reach targets. We performed a meta-analysis to compare the efficacy and safety of patient-led versus physician-led titration of basal insulin in patients with uncontrolled type 2 diabetes.Research design and methodsFour databases were searched from database inception through March 2020. Randomized controlled studies with at least 12 weeks of follow-up of patients with type 2 diabetes allocated to patient-led versus physician-led titration of basal insulin were selected. Data on glycemic endpoints (hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), hypoglycemia) and other outcomes (insulin dose, body weight, patient-reported outcomes, adverse events, rescue medication, discontinuation) were extracted. Data were pooled using a random-effects model.ResultsSix studies evaluating 12 409 patients were finally included. Compared with the physician-led performance, patient-led titration was associated with a statistically significant higher basal insulin dose (+6 IU/day), leading to benefits on HbA1c (−0.1%) and FPG (−5 mg/dL), despite a higher risk of any level hypoglycemia (relative risk=1.1) and a slight increase in body weight (+0.2 kg). No difference was found for the other outcomes.ConclusionsThe present study showed that patient-led titration of basal insulin was not inferior to physician-led titration in patients with uncontrolled type 2 diabetes. Therefore, diabetes self-management education and support programs on basal insulin should be widely adopted in clinical practice and patients provided with tools to self-adjust their dose when necessary.

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