Update (June 26, 2026): Lente vs NPH Insulin in Newly Diagnosed Diabetic Dogs — Fracassi et al. Randomised Trial

Bottom line.

• In a prospective, randomised, controlled clinical trial in 30 newly diagnosed diabetic dogs (Fracassi et al., Veterinary Record 2018), lente insulin and NPH (isophane) insulin administered every 12 hours were similarly effective; good glycemic control was achieved in 9/15 (60%) dogs in the lente group and 11/15 (73%) dogs in the NPH group at 12 weeks, a non-significant difference.¹
• Both groups showed significant improvement in polyuria, polydipsia, and blood glucose concentrations during the study; median final insulin dose per injection was 0.61 U/kg in the lente group and 0.49 U/kg in the NPH group.¹
• A subsequent 2019 review confirms isophane insulin is considered a highly suitable preparation for twice-daily treatment of diabetic dogs, with average effective doses of approximately 0.44 U/kg twice daily for larger dogs and 0.79 U/kg for small dogs reported in an earlier cohort study.²
• This is a clinician-facing evidence summary. It is not a dosing protocol; confirm regimen, monitoring and contraindications against current product labeling and a veterinary formulary.

Update context

This update summarises the only published randomised controlled trial directly comparing lente insulin and NPH insulin in dogs with newly diagnosed diabetes mellitus (Fracassi et al. 2018, Veterinary Record 183(8):262). Insulin type selection in canine diabetes is an area of active discussion; this trial provides the most robust comparative evidence available for these two commonly used preparations.

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What the evidence shows

Study design

This was a prospective, randomised, controlled clinical study enrolling 30 client-owned, newly diagnosed diabetic dogs.¹ Animals were randomised into two groups and received either lente insulin or NPH (neutral protamine Hagedorn / isophane) insulin administered subcutaneously every 12 hours. Follow-up re-evaluations were conducted at 1, 2, 4, 6, 8, and 12 weeks; at each visit, physical examination, blood glucose curve, and serum fructosamine concentrations were assessed.

Primary outcome: glycemic control at 12 weeks

At the end of the 12-week study, glycemic control was rated as good in:¹

• Lente group: 9 of 15 dogs (60%)
• NPH group: 11 of 15 dogs (73%)

The difference between groups was not statistically significant, supporting the conclusion that lente insulin and NPH insulin were similarly effective for treating dogs with newly diagnosed diabetes mellitus.¹

Clinical improvement in both groups

Both groups showed significant improvement in polyuria and polydipsia and blood glucose concentrations during the study period.¹ This finding is consistent with the known efficacy of twice-daily intermediate-acting insulin preparations in canine DM.

Insulin doses at study end

At the end of the study, the median insulin dose per injection was:¹

• Lente group: 0.61 U/kg (range 0.34–0.92 U/kg)
• NPH group: 0.49 U/kg (range 0.23–0.68 U/kg)

These values reflect the titrated maintenance doses reached after 12 weeks of monitoring and dose adjustment in newly diagnosed dogs. Do not use these figures as starting doses; starting doses and titration protocols must be taken from current product labeling and veterinary formularies.

Earlier cohort data on isophane insulin

An earlier uncontrolled cohort study of 54 diabetic dogs treated with isophane (NPH) insulin twice daily reported that 48 of 54 dogs were clinically healthy, alert, and free from symptoms of diabetes at the end of the study period.² Average effective doses were approximately 0.44 U/kg twice daily for larger dogs and 0.79 U/kg for smaller dogs. The study characterised isophane insulin as a highly suitable preparation for twice-daily treatment of diabetic dogs.²

Pharmacological context: lente vs NPH

Both lente insulin (porcine zinc suspension — e.g., Caninsulin/Vetsulin) and NPH/isophane insulin are intermediate-acting preparations administered subcutaneously twice daily in dogs. Lente insulin is a mixture of amorphous insulin zinc (30%) and crystalline insulin zinc (70%). NPH (isophane) insulin is composed of regular insulin complexed with protamine in a ratio that gives symmetrical, intermediate action. The pharmacokinetic profiles are broadly similar in dogs, consistent with the lack of difference in clinical outcomes in the Fracassi et al. trial.¹

Current guideline context

The 2026 AAHA Diabetes Management Guidelines for dogs are scheduled for release later in 2026. In the interim, the 2018 AAHA Diabetes Management Guidelines remain in effect for dogs. The Fracassi et al. 2018 randomised trial is the highest-quality comparative evidence available for insulin selection in newly diagnosed diabetic dogs, and its principal conclusion — that lente and NPH are similarly effective — informs current evidence-based practice.¹

How this fits clinical practice

The Fracassi et al. 2018 trial provides the most robust evidence that lente insulin and NPH insulin are interchangeable with respect to glycemic control outcomes in newly diagnosed diabetic dogs when both are administered every 12 hours with appropriate monitoring. The slightly lower median dose in the NPH group at 12 weeks and the numerically (though non-significantly) higher proportion achieving good control with NPH did not reach statistical significance in this 30-dog trial. The choice between lente and NPH in clinical practice is therefore guided by local availability, cost, owner compliance factors, and clinician experience rather than by a demonstrated superiority of one agent. Starting dose, monitoring protocol, and dose-adjustment algorithms should be taken from current product labeling, a veterinary formulary, and clinical judgment. Do not use the final-study doses reported here as starting doses.

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References

1. Fracassi F, Linari G. 2018. Comparison of lente insulin and NPH insulin therapy for the treatment of newly diagnosed diabetic dogs: a randomised study. Vet Rec 183(8):262. https://pubmed.ncbi.nlm.nih.gov/30030413/
2. The Use of Isophane Insulin for the Control of Diabetes Mellitus in Dogs. PMC article summarising 54-dog cohort; average dose 0.44 U/kg (large dogs) and 0.79 U/kg (small dogs). https://pmc.ncbi.nlm.nih.gov/articles/PMC8117837/

Changelog

• 2026-06-26: First published.