Lifestyle prevention is better than metformin! 4 new technologies and 9 new treatments for diabetes deserve attention

▎WuXi AppTec content team editor

Globally, 415 million people have diabetes, and an estimated 193 million people remain undiagnosed
.
Between 1980 and 2004, the incidence and prevalence of type 2 diabetes tripled
as obesity, sedentary lifestyles and population ageing deepened.
Diabetes, the sixth leading cause of disability globally (2015 statistics), puts considerable socio-economic pressure on individuals and is an important challenge
for global public health.

Recently, the famous medical journal "The Lancet" published a blockbuster review, focusing on diabetes prevention, screening testing, innovative technologies and new therapies
.
The review highlights that there are still many unanswered research questions in the field of diabetes treatment, with one of the most concerning being when therapies to cure type 2 diabetes will arrive
.
We believe that the relentless exploration of innovative technologies and new treatments will bring us hope
.

In addition, as we understand the pathophysiology of type 2 diabetes more and more, targeted therapies tailored to individuals with diabetes will also become a treatment trend
.

SCREENSHOT CREDIT: THE LANCET

Pathologic features of patients with type 2 diabetes include relative insulin deficiency (caused by islet β cell dysfunction) and insulin resistance in target organs
.
Cardiovascular disease is the largest cause of morbidity and mortality associated with type 2 diabetes, so people with diabetes need intensive management of blood sugar, lipids, and blood pressure to minimize
the risk of complications and disease progression.

The review notes that the treatment of patients with diabetes under 25 years of age is particularly challenging, with more complex phenotypes and may require decades of intensive management to minimize the occurrence and progression
of microvascular and macrovascular complications.
In addition, intensive management of older patients with diabetes (≥ 65 years) needs to be balanced
with clinical management of other comorbidities, cognitive impairment, and risk of hypoglycemia.

Prevention of type 2 diabetes: lifestyle prophylaxis is superior to metformin

Substantial research evidence suggests that obesity and impaired glucose regulation can be managed through diet and exercise interventions, and to a lesser extent pharmacological treatments (metformin and thiazolidinediones) to prevent the development
of type 2 diabetes.

In 3234 adults who were overweight or obese (with impaired glucose tolerance), intensive lifestyle modification (physical activity aimed at weight loss and a low-fat diet) reduced the risk of type 2 diabetes (58% relative risk reduction over a mean follow-up period of 2.
8 years) and was more effective than metformin or placebo
。 This benefit
was found in all participant populations regardless of sex, race, or genetic predisposition.

It should be noted that metformin was most effective in women with a history of gestational diabetes, while lifestyle interventions benefited the most
in people aged ≥60 years.
Data from the 15-year follow-up of the DPP study showed a 27% reduction in the incidence of diabetes in participants receiving lifestyle interventions and an 18%
reduction in participants treated with metformin.
In addition, the study also showed that normalization of glucose tolerance reduced the Framingham risk score (used to predict cardiovascular disease) by 2.
7% (p<0.
01)
after 10 years in people with prediabetes.

Notably, 318 million people are in preclinical diabetes with impaired glycemic regulation, and that intensive lifestyle modification, medication, or a combination of both can reverse or delay the development of
type 2 diabetes in this population.

Image source: 123RF

Management of type 2 diabetes mellitus: lifestyle intervention + hypoglycemic therapy

Individuals at risk associated with type 2 diabetes need to be actively screened to minimize the occurrence and progression
of microvascular and macrovascular complications.
Universal screening for diabetes in the population as a whole is not currently advocated, but rather a validated risk score is recommended for opportunistic screening and identification of people
at high risk for diabetes.
In these populations, fasting blood glucose, glycosylated hemoglobin (HbA1c) levels, or oral glucose tolerance can be confirmed
.

HbA1c levels are a robust diagnostic indicator
of type 2 diabetes.
Early detection of type 2 diabetes will help initiate patient-centered management that improves glycemic control and minimizes
the risk of complications.
The best management of diabetes today includes lifestyle interventions (eg, weight loss, increased physical activity levels, healthy eating, smoking cessation, moderate alcohol consumption) and glucose-lowering therapy to achieve individual glycemic goals
.

What are the outcomes of lifestyle interventions alone in people with type 2 diabetes? In the Look AHEAD study, more than 5000 patients with type 2 diabetes adopted intensive lifestyle modification strategies, yet after a median follow-up of 9.
6 years, this randomized controlled trial did not find significant improvement
in cardiovascular disease outcomes.

However, patients who received intensive lifestyle interventions experienced significant weight loss within 6 months, and associated improvements in waist circumference, HDL-C, and HbA1c levels
.
Not only that, the intervention also improved sexual dysfunction and depression in female patients, improved the quality of life of patients, and prevented and delayed the occurrence
of chronic kidney disease.

Innovative technologies and innovative therapies for type 2 diabetes

There are still many unanswered research questions in the field of diabetes treatment, the most concerned of which is when the treatment of type 2 diabetes will arrive
.
In the short term, we can achieve diabetes remission
through a very low-calorie diet or bariatric surgery.
However, these two interventions are difficult to implement at scale due to
limited population adaptation.
In terms of long-term treatment, in addition to traditional hypoglycemic drugs, the application of innovative technologies and innovative therapies may bring us more hope
for cure.

Innovative technology:

• In addition to the currently used insulin delivery methods, other insulin delivery methods, including biomimetic pancreas, are expected to help
  the management of type 2 diabetes in the coming years.
  

• Improved cardiovascular risk stratification can optimize patient outcomes, which may be achieved by adding cardiac biomarkers such as high-sensitivity troponin T and N-terminal brain natriuretic peptide precursors (NT-proBNP) to existing risk
  scores.
  

• The continuous glucose monitoring system can monitor blood glucose fluctuations for 24 hours, providing detailed and valuable information
  on the effectiveness of hypoglycemic therapy.
  However, the current accessibility of continuous glucose monitoring systems is somewhat limited
  .
  Scanning blood glucose monitors (Flash) are more accessible, easier to use, and require no calibration, or can be another effective option
  .
  

• CSII (Insulin Pump) is a well-researched insulin delivery device in patients with type 1 diabetes, but its widespread use
  in patients with type 2 diabetes is not currently advocated.
  Results from early trials suggest that insulin pumps can improve blood glucose stability and control levels, and that this effect can be enhanced by continuous glucose monitoring systems, particularly for postprandial blood glucose levels
  .
  Other insulin delivery methods currently under development include patch devices and inhalers, but the bioavailability, efficacy, and safety of these technologies need to be further evaluated
  .
  

In terms of innovative therapies:

• Stem cell research may pave the way for increasing the number of β cells, thereby delaying the progression of type 2 diabetes and additional glucose-lowering therapy
  .
  

• The brain and gut may be key organs
  that unleash the potential of diabetes treatment.
  Scientists are currently exploring the role
  of appetite-stimulating hormones (neuropeptide Y-Y, leptin, GLP-1) or appetite-stimulating factor inhibitors (ghrelin).
  In rodent models, the triple agonism of GLP-1, gastric inhibitory polypeptide, and glucagon receptors improved glycemic control and inhibited caloric intake
  .
  

• Glucagon receptor antagonists (e.
  g.
  , PF-06291874) are a new class of hypoglycemic drugs that have shown considerable therapeutic potential and are being evaluated in clinical trials for efficacy
  .
  These drugs reduce fasting blood glucose levels and mean daily blood glucose concentrations (over a 14-day period), and patients are at low risk of hypoglycemia
  .
  

• Other hypoglycemic therapies currently under development include fibroblast growth factor 21 analogues, adiponectin receptor agonists, cellular glucocorticoid inhibitors, selective PPAR modulators, oral hypoglycemic new drug imeglimin, and glucokinase activators
  。

A series of new types of therapies have become hot spots in recent years, such as cell/gene therapy, novel antibodies, RNA therapies, protein-degrading drugs, etc.
, which are expected to rewrite the future treatment landscape
.
To find out how much healthcare practitioners care about therapeutic innovation, we invite you to take 1 minute to fill out the questionnaire
.
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