An intensive, multifactorial treatment strategy targeting all known modifiable risk factors for vascular damage in patients with type 2 diabetes and microalbuminuria extends life expectancy by a median of almost 8 years over conventional diabetes care, according to long-term follow-up of the Steno-2 trial. Moreover, the treatment strategy essentially halves the risk of new cardiovascular complications over the ensuing 2 decades.
“In previous reports from the Steno-2 study, we have demonstrated the unprecedented efficacy of this structured, multifactorial intervention, where development of complications in the eyes, kidneys, legs, heart, and brain is halved compared with conventional multifactorial treatments,” first coauthor Jens Oellgaard, MD, University of Southern Denmark, Odense, said in a statement.
“This long-term follow-up of the Steno-2 study demonstrates beyond any doubt the sustainability of the intensified and multipronged treatment approach of type 2 diabetes patients with microalbuminuria introduced by us more than 21 years ago, [as] the benefit for patients in terms of a major extension of life and a halving of new cardiovascular complications speak for themselves,” one of the senior authors, Hans-Henrik Parving, MD, National University Hospital of Copenhagen, Denmark, added.
The follow-up study was published online August 16 in Diabetologia.
Original Steno-2 Trial
The Steno-2 trial was launched in 1993 with 160 patients with type 2 diabetes and microalbuminuria. The patients were randomly assigned to either conventional multifactorial treatment or to an intensified multifactorial treatment plan aimed at targeting risk factors for late diabetic complications.
“The originally intensified and very broad-spectrum Steno-2 treatment algorithm comprised individualized polypharmacy and behavior medication — prudent diet, exercise, and smoking cessation,” senior author Oluf Pedersen, MD, University of Copenhagen, Denmark, explained to Medscape Medical News in an email.
This strategy was accompanied by continuous patient education to keep participants motivated, he added.
However, as observed by first coauthor Peter Gaede, MD, University of Southern Denmark, the “marked risk reduction” Steno-2 trialists reported after 7.8 years of intensive therapy in the original trial meant it was unethical not to offer all remaining patients on conventional therapy the same intensified treatment plan.
21-Year Follow-up Available
Now, with a median follow-up of 21.2 years, Dr Gaede and colleagues are reporting the results for the follow-up cohort.
Between the initial report and the current follow-up, all patients, regardless of original study assignment, were offered the same intensive therapy. Thus, the new findings represent the long-term effect of following an intensive therapeutic plan for 7.8 years compared with a conventional treatment plan followed by an intensive plan.
At the latest follow-up in 2014, 48% of patients in the original intensive-therapy group had died compared with 69% in the original conventional-therapy group — meaning that patients originally randomized to the intensive-therapy group were 45% less likely to die than those in the original conventional-therapy group (hazard ratio [HR], 0.55; P = .005).
“Median survival time in the conventional-therapy group was 13.3 years, and the difference in median survival times after randomization was therefore at least 7.9 years,” Dr Gaede and colleagues report.
Tellingly, the median time to a patient’s first cardiovascular disease event or death was 16.1 years in the intensive-therapy group vs 8 years in the conventional-therapy group, suggesting that interventions targeting all modifiable risk factors for vascular damage had a major impact on cardiovascular risk.
This observation is underscored by the fact that death from cardiovascular causes was 62% lower in the intensive-therapy group and yet there was no between-group difference in mortality from noncardiovascular causes, the investigators note.
Specifically, 35 patients in the intensive-therapy group experienced a cardiovascular event compared with 51 patients in the conventional-therapy group.
This corresponds to a 51% relative risk reduction and a 20% absolute risk reduction for incident CVD in favor of intensive therapy.
“We also saw major sustainable reductions of microvascular complications in the eyes and kidneys,” Dr Pedersen said. Specifically, progression to retinopathy, autonomic neuropathy, and diabetic nephropathy occurred between approximately one-third to one-half as often in the intensive-therapy group compared with the conservative-therapy group.
Patients in the intensive-therapy group were also less than half as likely to go blind in at least one eye (P = .044) or progress to end-stage renal disease (P = .061).
“Recent epidemiological surveys now report on a decline in diabetes comorbidities and mortality in several parts of the world,” Dr Pedersen said.
“The observations from the 21 years of follow-up of the Steno-2 study are another important contribution to justify an early, intensified, individualized, and multifaceted care of patients with type 2 diabetes.”
Following a second report of the Steno-2 trial (N Engl J Med. 2008;358: 580-591), international guidelines integrated the experience from the Steno-2 trial into recommendations for the treatment of type 2 diabetes in general.
The study was funded by Novo Nordisk. Dr Pedersen has equity interest in Novo Nordisk; disclosures for the coauthors are listed in the article.
Diabetologia. Published online August 16, 2016. Article