Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats.

Maikawa CL, Chen PC, Vuong ET, Nguyen LT, Mann JL, d'Aquino AI, Lal RA, Maahs DM, Buckingham BA, Appel EA

Advanced science (Weinheim, Baden-Wurttemberg, Germany)9 Sept 2021Cited by 14 (Europe PMC)

PMID34499434PMCIDPMC8564421DOI10.1002/advs.202101575PepBankPUB-34499434

Summary

Dual-hormone replacement therapy with insulin and amylin in patients with type 1 diabetes has the potential to improve glucose management. Unfortunately, currently available formulations require burdensome separate injections at mealtimes and have disparate pharmacokinetics that do not mimic endogenous co-secretion. Here, amphiphilic acrylamide copolymers are used to create a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action. The co-formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h. The faster pharmacokinetics of monomeric insulin in this co-formulation result in increased insulin-pramlintide overlap of 75 ± 6% compared to only 47 ± 7% for separate injections. The co-formulation results in similar delay in gastric emptying compared to pramlintide delivered separately. In a glucose challenge, in rats, the co-formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations. Further, comparison of interspecies pharmacokinetics of monomeric pramlintide suggests that pharmacokinetics observed for the co-formulation will be well preserved in future translation to humans. Together these results suggest that the co-formulation has the potential to improve mealtime glucose management and reduce patient burden in the treatment of diabetes.

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

Results from this study5

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

Studies that did not test the peptide alone5

In this study, Pramlintide (Symlin) 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 Pramlintide (Symlin).

01AnimalNot a test of Pramlintide (Symlin) aloneAnimal study (in vivo)Pharmacokinetics
In diabetic rats, the co-formulation increased insulin-pramlintide pharmacokinetic overlap to 75 ± 6% versus 47 ± 7% with separate injections.
In plain wordsIn rats, the insulin-pramlintide formulation increased overlap of drug exposure compared with separate injections.
Peptide
Pramlintide (Symlin)
Outcome
IncreaseInsulin-pramlintide pharmacokinetic overlap
Study
ratn: not reported in source
Diabetic rats
Comparator
Separate injections
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
The faster pharmacokinetics of monomeric insulin in this co-formulation result in increased insulin-pramlintide overlap of 75 ± 6% compared to only 47 ± 7% for separate injections.
1 context sentence(design, population, supporting numbers)
Title · context
Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats.
In this study, Pramlintide (Symlin) 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 Pramlintide (Symlin).
Show in the study text Report a problemFND-3449943402
02AnimalNot a test of Pramlintide (Symlin) aloneAnimal study (in vivo)Efficacy outcome
In diabetic rats, the insulin-pramlintide co-formulation delayed gastric emptying similarly to separately delivered pramlintide.
In plain wordsIn rats, the insulin-pramlintide formulation and separately delivered pramlintide delayed stomach emptying similarly.
Peptide
Pramlintide (Symlin)
Outcome
No significant changeGastric emptying delay
Study
ratn: not reported in source
Diabetic rats
Comparator
Pramlintide delivered separately
Outcome group
Gastrointestinal motility · Gastrointestinal
Source sentences
Summary
The co-formulation results in similar delay in gastric emptying compared to pramlintide delivered separately.
1 context sentence(design, population, supporting numbers)
Title · context
Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats.
In this study, Pramlintide (Symlin) 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 Pramlintide (Symlin).
Show in the study text Report a problemFND-3449943403
03AnimalNot a test of Pramlintide (Symlin) aloneAnimal study (in vivo)Efficacy outcome
In rats undergoing a glucose challenge, the insulin-pramlintide co-formulation reduced glucose deviation from baseline versus insulin only.
In plain wordsIn rats, the insulin-pramlintide formulation reduced glucose changes after a glucose challenge compared with insulin alone.
Peptide
Pramlintide (Symlin)
Outcome
DecreaseGlucose deviation versus insulin only
Study
ratn: not reported in source
Diabetic rats
Comparator
Insulin only
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
In a glucose challenge, in rats, the co-formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations.
In this study, Pramlintide (Symlin) 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 Pramlintide (Symlin).
Show in the study text Report a problemFND-3449943404
04AnimalNot a test of Pramlintide (Symlin) aloneAnimal study (in vivo)Efficacy outcome
In rats undergoing a glucose challenge, the co-formulation reduced glucose deviation from baseline versus separate insulin and pramlintide administration.
In plain wordsIn rats, the formulation reduced glucose changes after a glucose challenge compared with separate insulin and pramlintide administration.
Peptide
Pramlintide (Symlin)
Outcome
DecreaseGlucose deviation versus separate administration
Study
ratn: not reported in source
Diabetic rats
Comparator
Separate insulin and pramlintide administration
Outcome group
Glycemic control · Metabolic and weight
Source sentences
Summary
In a glucose challenge, in rats, the co-formulation reduces deviation from baseline glucose compared to insulin only, or separate insulin and pramlintide administrations.
In this study, Pramlintide (Symlin) 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 Pramlintide (Symlin).
Show in the study text Report a problemFND-3449943405
05LabNot a test of Pramlintide (Symlin) aloneIn vitro (cell-free)Other
In laboratory aging tests, the insulin-pramlintide co-formulation remained stable beyond 16 hours, whereas commercial lispro aggregated in 8 hours.
In plain wordsIn lab tests, the insulin-pramlintide formulation remained stable longer than commercial lispro.
Peptide
Pramlintide (Symlin)
Outcome
IncreaseCo-formulation stability
Study
n: not reported in source
Stressed aging conditions
Comparator
Commercial insulin lispro
Outcome group
Formulation, delivery and stability · Pharmacology
Source sentences
Summary
The co-formulation is stable for over 16 h under stressed aging conditions, whereas commercial insulin lispro (Humalog) aggregates in 8 h.
1 context sentence(design, population, supporting numbers)
Summary · context
Here, amphiphilic acrylamide copolymers are used to create a stable co-formulation of monomeric insulin and amylin analogues (lispro and pramlintide) with synchronous pharmacokinetics and ultra-rapid action.
In this study, Pramlintide (Symlin) 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 Pramlintide (Symlin).
Show in the study text Report a problemFND-3449943401

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
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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