The metabolic effects of adding exenatide to basal insulin therapy when targeting remission in early type 2 diabetes in a randomized clinical trial.

Retnakaran R, Ye C, Emery A, Kramer CK, Zinman B

Nature communications16 Oct 2022Cited by 17 (Europe PMC)

PMID36244997PMCIDPMC9573864DOI10.1038/s41467-022-33867-9PepBankPUB-36244997

Summary

Combining a glucagon-like peptide-1 receptor agonist (GLP1-RA) with basal insulin is an emerging option when initiating injectable therapy in longstanding type 2 diabetes (T2DM). Recognizing that short-term insulin therapy can improve beta-cell function and induce glycemic remission in early T2DM, we hypothesized that adding the short-acting GLP1-RA exenatide to basal insulin in early T2DM may enhance the achievability of these outcomes. In this completed, 20-week, open-label, parallel-arm trial at an academic hospital, 103 individuals aged 30-80 years with <7 years duration of T2DM were randomized (by computer-generated sequence) to 8-weeks treatment with (i) insulin glargine (Glar; n = 33), (ii) glargine + thrice-daily lispro (Glar/Lispro; n = 35), or (iii) glargine + twice-daily exenatide (Glar/Exenatide; n = 35), followed by 12-weeks washout. The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide. Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control. Mean ISSI-2 over the 8-week intervention (primary outcome) did not differ across the groups (Glar/Exenatide 237 ± 11; Glar/Lispro 208 ± 11; Glar 223 ± 11; p = 0.19). Baseline-adjusted A1c at 8-weeks (secondary outcome) was lowest in Glar/Exenatide followed by Glar/Lispro and Glar (mean 5.9% vs 6.0% vs 6.2%; p = 0.0007). After 12-weeks washout, however, neither baseline-adjusted A1c nor baseline-adjusted ISSI-2 (secondary outcomes) differed between the groups, nor did (additional outcome) rates of remission (Glar/Exenatide 26.7%, Glar/Lispro 43.8%, Glar 32.1%; p = 0.35). There were no severe hypoglycemia episodes. In conclusion, adding exenatide to basal insulin in early T2DM does not further enhance underlying beta-cell function or the capacity to achieve diabetes remission, despite yielding on-treatment glycemic benefit.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study6

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone6

In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Exenatide (exendin-4).

01HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In early T2DM, ISSI-2 did not differ across treatment groups, including glargine/exenatide and glargine alone.
In plain wordsInsulin-producing cell function did not differ across groups, including exenatide plus glargine and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeISSI-2 during intervention
Study
n = 102
Comparator
Glargine and glargine/lispro
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Measurements
ISSI-2
237 score
glargine/exenatide
ISSI-2
208 score
glargine/lispro
ISSI-2
223 score
glargine
Source sentences
Summary
Mean ISSI-2 over the 8-week intervention (primary outcome) did not differ across the groups (Glar/Exenatide 237 ± 11; Glar/Lispro 208 ± 11; Glar 223 ± 11; p = 0.19).
2 context sentences(design, population, supporting numbers)
Summary · context
The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide.
Summary · context
Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3624499701
02HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In early T2DM, adjusted A1c was lowest with glargine/exenatide, followed by glargine/lispro and glargine, with an overall group difference.
In plain wordsAdjusted blood sugar was lowest with glargine/exenatide and highest with glargine alone, with an overall group difference.
Peptide
Exenatide (exendin-4)
Outcome
DecreaseA1c at 8 weeks
Study
n = 102
Comparator
Glargine and glargine/lispro
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Measurements
A1c
5.9%
glargine/exenatide
A1c
6%
glargine/lispro
A1c
6.2%
glargine
Source sentences
Summary
Baseline-adjusted A1c at 8-weeks (secondary outcome) was lowest in Glar/Exenatide followed by Glar/Lispro and Glar (mean 5.9% vs 6.0% vs 6.2%; p = 0.0007).
2 context sentences(design, population, supporting numbers)
Summary · context
The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide.
Summary · context
Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3624499702
03HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In early T2DM, adjusted A1c after washout did not differ across groups, including glargine/exenatide and glargine.
In plain wordsAfter treatment stopped, adjusted blood sugar did not differ across groups, including exenatide plus glargine and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeA1c after washout
Study
n: not reported in source
Comparator
Glargine and glargine/lispro
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
After 12-weeks washout, however, neither baseline-adjusted A1c nor baseline-adjusted ISSI-2 (secondary outcomes) differed between the groups, nor did (additional outcome) rates of remission (Glar/Exenatide 26.7%, Glar/Lispro 43.8%, Glar 32.1%; p = 0.35).
2 context sentences(design, population, supporting numbers)
Summary · context
The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide.
Summary · context
Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3624499703
04HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In early T2DM, adjusted ISSI-2 after washout did not differ across groups, including glargine/exenatide and glargine.
In plain wordsAfter treatment stopped, insulin-producing cell function did not differ across groups, including exenatide plus glargine and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeISSI-2 after washout
Study
n: not reported in source
Comparator
Glargine and glargine/lispro
Analysis
Secondary
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
After 12-weeks washout, however, neither baseline-adjusted A1c nor baseline-adjusted ISSI-2 (secondary outcomes) differed between the groups, nor did (additional outcome) rates of remission (Glar/Exenatide 26.7%, Glar/Lispro 43.8%, Glar 32.1%; p = 0.35).
2 context sentences(design, population, supporting numbers)
Summary · context
The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide.
Summary · context
Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3624499704
05HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialSafety outcome
In early T2DM, no severe hypoglycemia occurred in the trial, including the glargine/exenatide arm.
In plain wordsNo severe low blood sugar episodes occurred in the trial, including the exenatide combination group.
Peptide
Exenatide (exendin-4)
Outcome
Not applicableSevere hypoglycemia
Study
n = 102
Outcome group
Adverse events · Metabolic and weight
Source sentences
Summary
There were no severe hypoglycemia episodes.
2 context sentences(design, population, supporting numbers)
Summary · context
The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide.
Summary · context
Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3624499706
06HumanNot a test of Exenatide (exendin-4) aloneRandomized controlled trialEfficacy outcome
In early T2DM, remission rates after washout did not differ across groups, including glargine/exenatide and glargine.
In plain wordsDiabetes remission rates did not differ across groups, including exenatide plus glargine and glargine alone.
Peptide
Exenatide (exendin-4)
Outcome
No significant changeRemission after washout
Study
n: not reported in source
Comparator
Glargine and glargine/lispro
Outcome group
Glycemic control · Metabolic and weight
Measurements
Remission
26.7%
glargine/exenatide
Remission
43.8%
glargine/lispro
Remission
32.1%
glargine
Source sentences
Summary
After 12-weeks washout, however, neither baseline-adjusted A1c nor baseline-adjusted ISSI-2 (secondary outcomes) differed between the groups, nor did (additional outcome) rates of remission (Glar/Exenatide 26.7%, Glar/Lispro 43.8%, Glar 32.1%; p = 0.35).
2 context sentences(design, population, supporting numbers)
Summary · context
The analyzed population of 102 participants (median 3.5 years of T2DM, A1c 6.6% ±0.7%) consisted of 33 on Glar, 35 on Glar/Lispro and 34 on Glar/Exenatide.
Summary · context
Oral glucose tolerance tests at baseline, 4-weeks, 8-weeks and 20-weeks enabled assessment of beta-cell function (Insulin Secretion-Sensitivity Index-2 (ISSI-2)) and glycemic control.
In this study, Exenatide (exendin-4) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Exenatide (exendin-4).
Show in the study text Report a problemFND-3624499705

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22 Oct 2026, 02:26 UTC
Study results updated
Version 1
21 Oct 2026, 18:59 UTC
First added · source update from Europe PMC

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