Lapetus’ Understanding of Diabetes: The Example of Metformin

by | May 19, 2021

Estimating duration of life of individuals with any degree of precision requires a level of expertise that is rare. While one approach to survival analysis is to identify keywords in the medical records and to use the presence of those disease states to adjust the risk of death, the Lapetus approach to risk assessment is quite different.

In this Generian Newsletter, I’m going to provide you with a concrete example of how Lapetus scientists and physicians utilize our background and knowledge in medicine and public health and as scientists in the field of aging to generate a hyper-personalized life table for an individual that has been diagnosed with diabetes.

It has been shown that in general, diabetics live shorter lives than non-diabetics — Read More. Identifying someone as a diabetic from the medical record therefore seems like a logical way of adjusting the survival estimate for an individual with this disease. For example, it was demonstrated 43 years ago that after you control for age, systolic blood pressure, cholesterol, BMI, and smoking, the relative risk of death was 2.3 for diabetic men and 2.0 for diabetic women. While these relative risks have certainly changed since 1988, generating simple mortality multipliers based on this observation that are applied equally to all diabetics, is routine.

At Lapetus, we do not utilize generic mortality multipliers based on disease states identified in the medical record. We know from experience as physicians and scientists that there are multiple other mediating factors that influence how long a diabetic will live. One of the most important is the treatment protocol for diabetes that involves the use of Metformin.

Standard approach to estimating survival for a diabetic:

  • Upon verification of diagnosis of diabetes from the medical record, with no other relevant factors, choose a mortality multiplier of 2.3 for a man and adjust a VBT table accordingly to generate the LE.

  • Begin by generating a Summary Adjusted Life Expectancy (SALE) for the individual independent of disease diagnosis.
  • This provides us with an initial framework of estimated survival based on the unique inherited and acquired attributes of the individual(e.g., education, income, marital status, physical activity, BMI, smoking status, etc.) that have the potential to mediate duration of life apart from any disease states that might be present.
  • Send the SALE and medical records to a physician/scientist with experience in estimating survival for diabetics.

  • A Lapetus physician then reviews the medical records to determine how long ago the patient was diagnosed; what medications they’re taking (if any); what other disease states may be present that could influence survival with diabetes; what type of diabetes was diagnosed; patterns of weight loss and gain; whether the patient is allergic to any medications that could influence survival; and then the doctor attempts to determine whether the patient is compliant with the treatment protocol.

  • Lapetus physicians and population health experts are also on the lookout for the use of Metformin as a treatment for the patient’s diabetes. Why Metformin in particular? Scientists at Lapetus are affiliated with clinical trials that are about to begin that are testing Metformin as a potential therapeutic intervention to slow aging and extend life — Read More.

  • There is evidence in the scientific literature to suggest that diabetics taking Metformin live longer than non-diabetics — Read More — (see Figures 1 and 2). When we see this in the medical record, we make adjustments to our estimates of the risk of death depending on the presence or absence of other mediating factors that influence duration of life among diabetics.

Figure 1. All-cause mortality is lower among diabetics on metformin vs. non-diabetics. Source: Campbell et al. Aging Res Rev (2017) 30:31-44.


  • Standard approaches to estimating duration of life among diabetics are most often generic. They can miss the subtleties in the patient that influence survival with this disease.

  • Lapetus scientists are closely familiar with the latest research that links disease state, treatment protocols, and the newest drugs that have the potential to alter the course of survival in patients with a broad range of diseases, including diabetes.

  • Lapetus scientists are not just familiar with the treatments for various diseases, we are sometimes directly involved in clinical trials that are designed to test the effects of therapeutic interventions on survival.

  • The Lapetus approach to survival analysis is designed to

    • attain the most accurate assessment possible given the available information;

    • we utilize our expertise in medicine to zero in on the most important disease-specific risk factors that influence survival;

    • we bring to the analysis an assessment of the inherited and acquired risk factors that can influence survival for patients with a given disease; 

    • and then we blend these two approaches to generate our final estimate of LE. 

  • It is possible that Lapetus will find the expected LE of a patient with diabetes to be higher than the survival of a non-diabetic patient depending on the unique circumstances faced by the patient. This is unlikely to occur with traditional methods of risk assessment, but the patient’s medical record may clearly justify such a conclusion.

  • Estimated survival among patients with diabetes is just one of many examples of how Lapetus physicians and population scientists marshall all of our technical expertise during the assessment process in our pursuit of accuracy and stability.

In subsequent newsletters, we’ll illustrate how the Covid pandemic compares to previous pandemics; we’ll demonstrate how the mRNA technology that led to our current suite of vaccines, could be a game changing technology that influences life settlement markets (and our mortality assumptions) in the coming years and decades; and we’ll discuss how advances in aging science could lead to therapeutic interventions that slow aging.