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The UKPDS (United Kingdom Prospective Diabetes Study) was a huge study undertaken in the UK to see if intensive blood glucose lowering in T2D would prevent end organ damage over long run. The DCCT study mentioned previously had already established the paradigm of tight blood sugar control in Type 1, but whether this held true for type 2 remained to be seen.
3867 newly diagnosed T2D patients who failed a 3 month lifestyle therapy trial were enrolled into an intensive group with sulfonlyureas or insulin versus conventional control (UKPDS 33). The intensive group would target a fasting glucose of less than 6.0 mmol/L. In the conventional group, drugs were only added if FBG exceeded 15. If high blood sugars was the primary cause of disease, then this intensive group should do better. We can move the sugar from the blood into the body with drugs, but the price to be paid is excessively high insulin levels. Remember that these T2D patients had a baseline level of insulin that was already high. We would raise them even further in order to lower blood sugars.
The drugs certainly were successful at lowering blood sugars. Over the 10 years of the study, the average HgbA1C was 7.0% in the drug group compared to 7.9% in the diet group. But there was a price, too. Weight gain was far worse on the drug group (an excess of 2.9 kg) and in particular, the insulin group – averaging 4 kg excessive weight gain. Low blood sugars – hypoglycaemia was also significantly increased. These, however were expected, but as discussed before, there is concern that excessive weight gain will lead to worse outcomes down the line.
The results surprised most physicians at the time. Expecting a slam dunk, there was instead some minor benefit for eye disease but they were unable to find any kind of benefits for the end points that everybody was interested in – cardiovascular disease, including heart attacks and strokes. The results were stunning. Despite reducing blood sugars, CV disease showed no benefits.
This was more than just a trivial result. Since the majority of deaths are due to CV disease, the primary goal of therapy was reduction in deaths and CV disease, not microvascular disease.
Metformin was considered separately in sub study UKPDS 34. Here 753 overweight patients with T2D were randomized to either metformin or diet control alone. Once again, over the space of over 10 years, the average blood sugar was lowered by metformin to 7.4% compared to an A1C of 8% in the conventional group. In contrast to the previous study, intensive control with metformin showed a substantial improvement in clinically important outcomes – there was a 36% decrease in death (all cause mortality) as well as a 39% decrease in risk of heart attack. That’s a very significant benefit. Metformin performed far better than the insulin/ SU group despite the fact that average blood sugar control was worse.
Read more here: https://intensivedietarymanagement.com/ukpds-futility-blood-sugar-lowering-t2d/
3867 newly diagnosed T2D patients who failed a 3 month lifestyle therapy trial were enrolled into an intensive group with sulfonlyureas or insulin versus conventional control (UKPDS 33). The intensive group would target a fasting glucose of less than 6.0 mmol/L. In the conventional group, drugs were only added if FBG exceeded 15. If high blood sugars was the primary cause of disease, then this intensive group should do better. We can move the sugar from the blood into the body with drugs, but the price to be paid is excessively high insulin levels. Remember that these T2D patients had a baseline level of insulin that was already high. We would raise them even further in order to lower blood sugars.
The drugs certainly were successful at lowering blood sugars. Over the 10 years of the study, the average HgbA1C was 7.0% in the drug group compared to 7.9% in the diet group. But there was a price, too. Weight gain was far worse on the drug group (an excess of 2.9 kg) and in particular, the insulin group – averaging 4 kg excessive weight gain. Low blood sugars – hypoglycaemia was also significantly increased. These, however were expected, but as discussed before, there is concern that excessive weight gain will lead to worse outcomes down the line.
The results surprised most physicians at the time. Expecting a slam dunk, there was instead some minor benefit for eye disease but they were unable to find any kind of benefits for the end points that everybody was interested in – cardiovascular disease, including heart attacks and strokes. The results were stunning. Despite reducing blood sugars, CV disease showed no benefits.
This was more than just a trivial result. Since the majority of deaths are due to CV disease, the primary goal of therapy was reduction in deaths and CV disease, not microvascular disease.
Metformin was considered separately in sub study UKPDS 34. Here 753 overweight patients with T2D were randomized to either metformin or diet control alone. Once again, over the space of over 10 years, the average blood sugar was lowered by metformin to 7.4% compared to an A1C of 8% in the conventional group. In contrast to the previous study, intensive control with metformin showed a substantial improvement in clinically important outcomes – there was a 36% decrease in death (all cause mortality) as well as a 39% decrease in risk of heart attack. That’s a very significant benefit. Metformin performed far better than the insulin/ SU group despite the fact that average blood sugar control was worse.
Read more here: https://intensivedietarymanagement.com/ukpds-futility-blood-sugar-lowering-t2d/
