Insulin and metformin in combination cut mortality in type 2 diabetes

Study of 12,020 people finds that taking metformin with insulin reduces risk of major adverse cardiac events compared with insulin only.

Metformin tablet

People with type 2 diabetes who take metformin with insulin have a reduced risk of major adverse cardiac events (MACE) and death compared with those treated with insulin alone, according to a study carried out at Cardiff University and published in PLoS One on 6 May 2016[

While metformin lowers the dose of insulin that is required, previous research has suggested that a combination regimen may improve outcomes for patients[2]
. To understand more about this, researchers, in collaboration with the Cardiff-based healthcare data consultancy Pharmatelligence, carried out a retrospective cohort study, collecting outcome data from the UK Clinical Practice Research Datalink on 12,020 people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards.

“We examined insulin dose along with the impact of combining insulin with metformin,” says Craig Currie, lead author and professor of applied pharmacoepidemiology at Cardiff University’s School of Medicine. “We found that there was a considerable reduction in deaths and heart problems when this cheap and common drug was used in conjunction with insulin.”

The team used all-cause mortality as a primary outcome, but also looked at the incidence of MACE (myocardial infarction or stroke) and cancer, following the patients over an average of 3.5 years to the first of these outcomes, or the date when they changed medication.

Patients treated with both insulin and metformin had a reduced risk of MACE or death (adjusted hazard ratios 0.75, 95% confidence interval [CI] 0.62–0.91, and 0.60, CI 0.52–0.68, respectively) when compared with the individuals receiving only insulin. There was no significant difference in rates of cancer.

Simon O’Neill, director of health intelligence and professional liaison at the charity Diabetes UK, says the study supports the use of metformin and insulin as treatment options for people with type 2 diabetes. “Type 2 diabetes is initially treated with a healthy diet and increased physical activity, but as it is a progressive condition, blood glucose lowering medication, such as metformin and insulin, may be required over time,” he says. “Sometimes insulin and metformin are used together, but it’s important to note that the type of medication required to treat type 2 diabetes will vary according to each individual’s need.”

Individuals with type 2 diabetes who need insulin therapy are increasingly being treated with metformin: in 1991, the vast majority of people with type 2 diabetes used insulin as a monotherapy, whereas by 2010, 42% of patients were treated with insulin and metformin in combination.

The researchers suggest the need for further studies to determine the risks and benefits of insulin in type 2 diabetes and the possible benefits associated with the administration of concomitant metformin. O’Neill supports this conclusion: “We need to see further research and clinical trials in this area before we can say for definite that metformin combined with insulin should be used as a first line of treatment for everyone diagnosed with type 2 diabetes.”

  • This article was amended on 3 January 2016 to correct an error – the study did not show that people with type 2 diabetes who take metformin with insulin have a reduced risk of cancer compared with those treated with insulin alone.


[1] Holden SE, Jenkins-Jones S & Currie CJ. Association between insulin monotherapy versus insulin plus metformin and the risk of all-cause mortality and other serious outcomes: a retrospective cohort study. PLoS One 2016:11;e0153594. doi: 10.1371/journal.pone.0153594

[2] Currie CJ, Poole CD, Evans Met al. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. J Clin Endocrinol Metab 2013:98;668-77. doi: 10.1210/jc.2012-3042

Last updated
The Pharmaceutical Journal, Insulin and metformin in combination cut mortality in type 2 diabetes;Online:DOI:10.1211/PJ.2016.20201133

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