Shared decision-making approach to type 2 diabetes management

Blair J. MacDonald; James P. McCormack; Ricky D. Turgeon

doi:10.46747/cfp.7005310

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The data presented to patients for decision aid must be reliable
Rémy Boussageon

Published on: 09 May 2025

Published on: (9 May 2025)
Page navigation anchor for The data presented to patients for decision aid must be reliable
The data presented to patients for decision aid must be reliable
Rémy Boussageon, General Practicionner, University of Lyon 1, Lyon, France
We read with interest the article by MacDonald et al. on decision support for type 2 diabetic patients (1). This decision aid is a breakthrough in patient support, as it is the first to present the absolute risk of major diabetic complications without treatment, and with treatment, thus meeting certain quality criteria promoted by IPDAS (2).

We would like to promote it in France among general practitioners, to change the therapeutic paradigm from a “treat to target” approach focused on achieving an Hba1c target, to a “risk reduction” approach, better suited to information sharing and informed decision-making (3) and, above all, more in line with evidence-based data (4-5).

But first, it's important that the data presented be valid. We do not understand how the source studies justifying the benefits of the drugs presented were selected. We'll illustrate this with two examples: “metformin reduces the risk of stroke by 30%, and aspirin reduces the relative risk of stroke or MI (ASCVD) by 10%” (1).

According to the references, the site mentions 3 studies: UKPDS 34 (6) and its follow-up (7) , as well as the networked meta-analysis by Shi et al. (8).
The meta-analysis by Shi et al. concludes that metformin has not proved effective in reducing the risk of macro- and microvascular complications (8). It is consistent with previous meta-analyses (9-12).

Thus, the authors base their conclusions primarily on the UKPDS 34 (6) study and it...
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We read with interest the article by MacDonald et al. on decision support for type 2 diabetic patients (1). This decision aid is a breakthrough in patient support, as it is the first to present the absolute risk of major diabetic complications without treatment, and with treatment, thus meeting certain quality criteria promoted by IPDAS (2).

We would like to promote it in France among general practitioners, to change the therapeutic paradigm from a “treat to target” approach focused on achieving an Hba1c target, to a “risk reduction” approach, better suited to information sharing and informed decision-making (3) and, above all, more in line with evidence-based data (4-5).

But first, it's important that the data presented be valid. We do not understand how the source studies justifying the benefits of the drugs presented were selected. We'll illustrate this with two examples: “metformin reduces the risk of stroke by 30%, and aspirin reduces the relative risk of stroke or MI (ASCVD) by 10%” (1).

According to the references, the site mentions 3 studies: UKPDS 34 (6) and its follow-up (7) , as well as the networked meta-analysis by Shi et al. (8).
The meta-analysis by Shi et al. concludes that metformin has not proved effective in reducing the risk of macro- and microvascular complications (8). It is consistent with previous meta-analyses (9-12).

Thus, the authors base their conclusions primarily on the UKPDS 34 (6) study and its follow-up (7). But in the UKPDS study, there was no evidence that metformin was effective in reducing the risk of stroke.

Furthermore, the UKDPS34 study is at very high risk of bias (13):

- The study was not double blinded, and no placebo was administered to the control group. This could result in problems such as differing approaches to treatment, concomitantly administered treatments, and divergent outcome assessments. Although this remains controversial, it is possible that unblinded studies have a general tendency to overestimate the efficacy of the treatments studied, including on total mortality (14).

- Change in statistical significance after results are known.

Moreover, the concluding publication indicates that a significance threshold of 1% (p < 0.01) was initially chosen This was changed after the 1987 analysis to 5% (P<0.05) for the three main composite criteria. The positive results achieved with metformin for total mortality and myocardial infarction in UKPDS 34 are above the initial threshold (P=0.017 and P=0.011, respectively). Changing the significance values during the study and with the knowledge of the results increases the probability that the results are due to chance alone.

- Multiplicity

Multiple analyses and alpha risk inflation are also a problem that was not taken into account at the outset of the study. With UKPDS 33 and 34, there were more than 100 statistical analyses. As chance alone will give a positive result in 5/100 tests at 5% significance and 1/100 at 1% significance, the possibility of the metformin result being down to chance cannot be ruled out.

- Its results have never been reproduced.

In science, the replication criterion is essential to confirm results, especially when they are impressive. Indeed, the spectacular results on total mortality (NNT = 14 and p = 0.01) contribute to the belief that metformin is effective. However, it is quite possible to observe a difference in total mortality that is linked to chance alone. For example, in the PRAISE 1 study, amlodipine in heart failure showed a benefit on total mortality in a subgroup study (15. This result was not confirmed in the more powerful PRAISE 2 study16.

And UKPDS 34 has never been replicated.

Aspirin

The only study cited to justify the efficacy of aspirin is the ASCEND trial, whose primary endpoint was modified during the course of the study due to lack of power (17). The “transient ischemic attack” (TIA) criterion was added and follow-up extended. In the end, only the composite endpoint including TIAs was statistically significant (HR = 0.88; IC95% [0.79 - 0.97], p = 0.01); the endpoint without TIAs was not significant.

Meta-analyses evaluating the efficacy of aspirin in primary prevention in type 2 diabetic subjects generally show that efficacy is uncertain, possible on a composite endpoint of cardiovascular events in high-risk cardiovascular patients but not in low-risk patients, and not on each individual endpoint (18-20). In addition, the upper bound of the confidence interval is close to 1, consistent with no effect. There is also a possible publication bias with the ACCEPT-D trial, for which it is not known whether it has begun, is ongoing or has been completed (21).

Last but not least, in ASCEND and in these meta-analyses, the risk of serious bleeding is similar in terms of absolute risk (around 1%) to the eventual benefit (around 1%), i.e. the average net benefit is zero; and unfavorable if we take into account aspirin's other adverse effects (minor bleeding, epigastralgia, allergy, etc.). For this reason, many clinical practice guidelines do not recommend aspirin for primary prevention in type 2 diabetic patients.

Conclusion

Even if we recognize a certain subjectivity in the interpretation of “medical evidence ” (22) , we feel it is necessary to define a priori what constitutes sufficiently convincing evidence to be presented to patients as an aid to decision-making.

We are available to work with the authors on this project.

References

1. MacDonald BJ, McCormack JP, Turgeon RD. Shared decision-making approach to type 2 diabetes management. Can Fam Physician 2024;70(5):310-315.

2. Elwyn G, O'Connor AM, Bennett C, Newcombe RG, Politi M, et al. Assessing the Quality of Decision Support Technologies Using the International Patient Decision Aid Standards instrument (IPDASi). Plos One 2009 ; 4(3): e4705

3. Rodríguez-Gutiérrez R, Millan-Alanis JM, Barrera FJ, McCoy RG. Value of Patient-Centered Glycemic Control in Patients with Type 2 Diabetes. Curr Diab Rep 2021; 21(12):63.

4. Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassaï B, Erpeldinger S, Wright JM, Gueyffier F, Cornu C. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 2011 ;343:d4169. doi: 10.1136/bmj.d4169.

5. Rodriguez-Gutierrez R, Gonzalez-Gonzalez JG, Zuñiga-Hernandez JA, McCoy RG. Benefits and harms of intensive glycemic control in patients with type 2 diabetes. BMJ 2019 ;367:l5887.

6. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998 ;352(9131):854-65.

7. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008 ;359(15):1577-89.

8. Shi Q, Nong K, Vandvik PO, Guyatt GH, Schnell O, Rydén L, Marx N, et al. Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ 2023;381:e074068.

9. Boussageon R, Supper I, Bejan-Angoulvant T, Kellou N, Cucherat M, Boissel JP, et al. Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials. PLoS Med 2012;9(4):e1001204.

10. Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia 2017;60(9):1620-1629.

11. Gnesin F, Thuesen ACB, Kähler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev 2020 Jun 5;6(6):CD012906.

12. Gerardo González-González J, Cesar Solis R, Díaz González-Colmenero A, Raygoza-Cortez K, Moreno-Peña PJ, Sánchez AL, McCoy RG, et al. Effect of metformin on microvascular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Res Clin Pract 2022 ;186:109821.

13. Boussageon R, Gueyffier F, Cornu C. Metformin as firstline treatment for type 2 diabetes: are we sure? BMJ 2016 ;352:h6748.

14. Savovic J, Turner RM, Mawdsley D, Jones HE, Beynon R, Higgins JPT, Sterne JAC. Association Between Risk-of-Bias Assessments and Results of Randomized Trials in Cochrane Reviews: The ROBES Meta-Epidemiologic Study. Am J Epidemiol 2018; 187(5):1113-1122.

15. Packer M, O'Connor CM, Ghali JK, Pressler ML, Carson PE, Belkin RN, Miller AB, Neuberg GW, Frid D, Wertheimer JH, Cropp AB, DeMets DL. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med 1996 ;335(15):1107-14.

16. Packer M, Carson P, Elkayam U, Konstam MA, Moe G, O'Connor C, Rouleau JL, Schocken D, Anderson SA, DeMets DL; PRAISE-2 Study Group. Effect of amlodipine on the survival of patients with severe chronic heart failure due to a nonischemic cardiomyopathy: results of the PRAISE-2 study (prospective randomized amlodipine survival evaluation 2). JACC Heart Fail 2013 ;1(4):308-314

17. ASCEND Study Collaborative Group; Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med 2018 ;379(16):1529-1539.

18. Liu S, Eckstein J, Lam A, Cheema AN. Acetylsalicylic Acid (Aspirin) for Primary Prevention of Cardiovascular Events in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Vasc Pharmacol. 2023;21(2):111-119..
19. Masson W, Barbagelata L, Lavalle-Cobo A, Lobo M, Masson G, Nogueira JP, Vergès B. Low-doses aspirin in the primary prevention of cardiovascular disease in patients with diabetes: Meta-analysis stratified by baseline cardiovascular risk. Diabetes Metab Syndr 2022;16(1):102391.

20. Kheiri B, Barbarawi M, Bachuwa G, Shapiro MD. Aspirin for Primary Prevention of Cardiovascular Disease. Circ Cardiovasc Qual Outcomes 2019 ; 12(6):e005846.

21. De Berardis G, Sacco M, Evangelista V, Filippi A, Giorda CB, Tognoni G, Valentini U, Nicolucci A; ACCEPT-D Study Group. Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): design of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. Trials. 2007 Aug 28;8:21. doi: 10.1186/1745-6215-8-21.

22. Bauchner H, Ioannidis JPA. The Subjective Interpretation of the Medical Evidence. JAMA Health Forum 2024;5(3):e240213.
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Competing Interests: None declared.