silaja cheruvu, r3. what’s the best way to prevent diabetes in high risk patients? by doing...

Silaja Cheruvu, R3

What’s the BEST way to prevent diabetes in high risk patients?

By doing nothing? With lifestyle changes? With medication?

27 centers 1996-1999 3234 participants “High Risk”

◦ 25 years old◦ BMI>24◦ Elevated fasting glucose, 2 hour GTT

Placebo arm=Standard lifestyle recommendations

Metformin arm Troglitazone arm (discontinued early) Intensive Lifestyle Modification arm

◦ Achieve/maintain a 7% weight loss◦ 150 minutes/week◦ 16 week curriculum

Placebo arm◦ 77%

Metformin arm◦ 72%

Intensive Lifestyle Modification arm◦ 50% reached goal weight loss◦ 38% kept the weight off◦ 74% were exercising at 24 weeks◦ 58% kept exercising

Crude Incidence (person-years)◦ Placebo: 11◦ Metformin: 7.8◦ ILM: 4.8

Cumulative Incidence (over 3 years)◦ Placebo: 28.9 %◦ Metformin: 21.7 %◦ ILM: 14.4 %

Incidence of DM was REDUCED by 31% (CI: 17-43) in metformin arm

Incidence of DM was REDUCED by 58% (CI: 48-66) in ILM arm

NNT◦ Metformin: 13.9 (CI: 8.7-33.9)◦ ILM: 6.9 (CI: 5.4-9.5)

Were the patients randomized? Was randomization concealed? Were patients similar in prognostic factors?

◦ Table 1 Was the study blinded? How complete was the follow-up? Was the study stopped early? Intention to treat?

Absolute Risk Reduction◦ ARR = CER – EER◦ CER = 28.9%◦ EER = 14.4%

ARR = 28.9% - 14.4% = 14.5%

In those patients who are high risk for developing DM, when followed for 3 years, 14.3% fewer develop DM if they participate in ILM compared to placebo.

Relative Risk Reduction◦ RRR = (CER – EER ) /CER x 100 ◦ CER= 28.9◦ EER=14.4◦ (28.9% - 14.4%) / 28.9 % x 100 = 50%

Over a 3 year period, there is a 50% decrease in the incidence of DM in ILM group when compared to the placebo group.

Number Needed to Treat (ILM)◦ NNT=1/ ARR◦ 1/0.145 = 7

Number Needed to Treat (metformin)◦ NNT=1/ARR◦ 1/0.072 = 14

In order to prevent 1 case of DM over a 3 year period, you would have to treat 7 people with the intensive lifestyle modifications and 14 people with metformin.

Confidence Intervals and Precision◦ Number Needed to Treat

ILM: NNT=7 (CI: 5.4 to 9.5) Metformin: NNT=14 (CI: 8.7 to 33.9)

ILM arm is more precise than metformin arm but both are statistically significant.

UNM, Shiprock and Zuni◦ DIPS in Zuni

No subgroup analysis of high HbA1Cs vs low HBA1Cs

Subgroup analysis◦ Metformin arm NOT statistically significant in

Hispanics and Native Americans

Good study BUT it’s a surrogate outcome

Only followed for 3 years…◦ Blinded arm terminated early

Even with LOW adherence, ILM works!◦ …but so does metformin!

POLICY CHANGE◦ Can our patients exercise and do they access to

healthy foods?