The reason behind the guidelines that recommended lower HbA1c targets (<7% or <6.5%) is that more intensive blood sugar control would reduce risks for cardiovascular, cerebrovascular, neurologic, ophthalmologic, and renal complications. However, the evidence for reduction is inconsistent, and reductions were seen only in surrogate microvascular measures such as the presence of excess proteins in the urine. 

Clinical trials show that achieving an HbA1c between 7% and 8% will best balance long-term benefits with harms such as low blood sugar, other medication-related adverse effects, medication burden, and costs.

The ACCORD trial, which targeted an HbA1c <6.5% and achieved the lowest target HbA1c level of the included studies (6.4%), was discontinued early because of increased overall death, cardiovascular mortality, and severe low blood sugar events. 

The VADT study in 2009 found that intensive glucose (blood sugar) control in older men with longstanding type 2 diabetes did not significantly reduce their risk of major cardiovascular (CV) events, including heart attack, stroke, and death from CV causes, compared with standard blood sugar control.

Researchers recently reported 15-year follow-up results from VADT. They found that intensive blood sugar control did not exert any “legacy effect”: the intensive blood sugar control group did not enjoy CV benefits 15 years after the start of the study.

The ADVANCE study also failed to find a statistically significant clinical benefit and had more adverse effects with an achieved median HbA1c of 6.4% vs 7.0%. In addition, more intensive treatment to achieve a lower target is more costly and associated with increased patient burden.

The UKPDS 33 trial showed that treatment to a target of about 7% with a sulfonylurea and insulin if needed in adults with newly diagnosed diabetes did not reduce the risk of any diabetes-related end point or all-cause mortality after 10 years but was associated with a small absolute reduction in these outcomes after 17 years of follow-up.

A sub-study (UKPDS 34) also showed a modest reduction in diabetes-related end points and all-cause mortality with metformin treatment in overweight or obese adults (median  HbA1c achieved was 7.4%).

Recent Danish register-based cohort study (August 12, 2021) including 52,523 people who died aged 80 years or older between 2006 and 2018, having had type 2 diabetes for a median of 9 years found that, over two-thirds of the participants had one or more diabetes complication at the time of death, most commonly cardiovascular, hypertensive, or kidney disease.

While we acknowledge the damage caused by glucotoxicity, we ignore the insulin toxicity. Multivariate analysis of the EuroDiab study revealed the stunning conclusion that glucotoxicity, as measured by Hemoglobin A1C was not a significant risk factor. 

Multiple other studies confirmed the EuroDiab results. The Golden Years Cohort Study followed 400 type 1 diabetic patients who lived over 50 years managing their disease. This group had beaten the odds and survived. What was their secret? One thing became clear.

The secret was not tight blood glucose control.

The Golden Cohort’s average A1C was 7.6% — well over the standard recommended target of 7.0%. This level could only be described according to standard management as ‘poor’. Some had A1C measurements in the 8.5–9.0% range, yet still far out-lived the average. Strikingly, no Golden Cohort patient had an A1C in the normal range!

Clearly, glucotoxicity was not the major player here.

Recently on march 2018 a new set of global guidelines have been developed to manage diabetes. American College of Physicians (ACP) recommends moderate blood sugar control targets for most patients with type 2 diabetes. 

American College of Physicians (ACP) is asking clinicians to treat adults with Type 2 diabetes less aggressively and targets a Haemoglobin A1c (HbA1c is a test that represents blood glucose control over the preceding three months) of 7% to 8%, against the current recommendation of below 6.5%. It asks clinicians to deintensify drug therapy in patients with HbA1c levels of less than 6.5%.

The new guidance from the American College of Physicians (ACP) supporting higher glycated hemoglobin (HbA1c) targets for pharmacotherapy in adults with type 2 diabetes (T2D), published in the Annals of Internal Medicine, has been the target of criticism from several diabetes organizations including indian doctors.

But till date ADA and AACE guideline is in deep contrast with the ACP 2018 guideline which recommends a HbA1c between 7%-8% for most patients. (6,7,8

A 2021 meta-analysis convincingly highlights that the maximum macrovascular benefits, by way of reduction of non-fatal MI, non-fatal stroke and all-cause mortality are achieved with a target HbA1C between 7 – 7.7%, whether the duration of T2D is less than or more than 10 years. This is in keeping with the ACP guidelines. Physicians should therefore aim for a target HbA1C of 7 – 7.7% regardless of which molecule is used for the treatment of T2D to improve the macrovascular outcomes of T2D.

 ACP guidance focuses on the following four recommendations:

  1. Personalized treatment to minimize harms. Clinicians should personalize goals for glycemic control in patients with type 2 diabetes on the basis of a discussion of benefits and harms of pharmacotherapy, patients’ preferences, patients’ general health and life expectancy, treatment burden, and costs of care.
  2. Target HbA1c to between 7%-8%Clinicians should aim to achieve an HbA1c level between 7% and 8% in most adults with type 2 diabetes.
  3. Back off on intensive treatment. Clinicians should consider de-intensifying pharmacologic therapy in patients with type 2 diabetes who have achieved HbA1c levels less than 6.5%.
  4. Treat older patients’ hyperglycemia. Clinicians should avoid targeting HbA1c levels in patients with a life expectancy less than 10 years due to advanced age (80 years or older), residence in a nursing home, or chronic conditions (such as dementia, cancer, end-stage kidney disease, or severe chronic obstructive pulmonary disease or congestive heart failure) because the harms outweigh the benefits in this population.

According to Studies reported by Tight Glycemic Control for Type 2 Diabetes (Over Five Years) does not reduce deaths, heart attacks, strokes, or kidney failure. 

So, why do some of us still obsess over blood glucose numbers in Type 2 Diabetes ?

Unfortunately, it’s likely because diabetes specialists have not yet understood that this disease is about hyperinsulinemia, not hyperglycaemia. The drug companies, on the other hand, are all to happy to leave the status quo, which is extraordinarily profitable for them.