To the three well-known antidiabetic treatment classes of the early 2000s, many new therapies with remarkable efficacy and safety have been added, many of them with significant pleiotropic effects (mainly GLP-1 agonists and SGLT-2 inhibitors).
Remarkable new therapeutic categories
“Of the existing treatment categories, we point out the most reliable and those that are worth mentioning.”
• The new molecules of weekly GLP-1 agonists (semaglutide, albiglutide) of which semaglutide has already been added to the therapeutic arsenal. Semaglutide is a potent weekly GLP-1 agonist with excellent efficacy data (1.4-1.6% reduction in glycosylated hemoglobin, 4-5kg reduction in body weight) and safety in SUSTAIN studies.
• The first GLP-1 tablet (oral semaglutide) for which many PIONEER phase 3 studies have shown particular efficacy (in glycemic control and weight loss) and safety and its release is expected. GLP-1 agonists act on the GLP-1 receptors of various organs and, thus, have an action similar to the incretin hormone GLP-1, but many times more potent than the action of endogenous GLP-1. GLP-1 agonists have antihyperglycemic, antihypertensive, cardioprotective effects and reduce body weight, while one of them (liraglutide) also reduces the risk of fatal events.
“Regarding SGLT-2 inhibitors, we also point out this very prominent and extremely recent anti-diabetic treatment.”
• The new studies (DAPA HF, EMPEROR red., EMPEROR pres, CREDENCE) of SGLT-2 inhibitors that showed the unquestionable cardioprotective (mainly in reducing the risk of hospitalization for heart failure even in non-diabetics with heart failure and retention with reduced ejection fraction) and nephroprotective action, while of course the very significant reduction of the risk of fatalities (38%) offered by empagliflozin is known.
We note the very recent good action and safety data that appear in the studies SOLOIST-WHF and SCORED the sotagliflozin-inhibitor SGLT-2 and SGLT-1 (while the SGLT-2 receptors are in the proximal coated renal tubules, the SGLT -1 is in the epithelial intestinal cells), which seems to increase the efficacy of sotagliflozin. In these studies, sotagliflozin showed a significant reduction in the risk of hospitalization for heart failure and a reduction in the risk of cardiovascular death in patients with heart failure with sustained ejection fraction as well as a significant reduction in the risk of myocardial infarction or myocardial infarction.
Remarkable upcoming therapeutic categories
“We also note, in the context of future anti-diabetic categories, the double fighter GLP-1 / GIP. The dual agonist will act on the receptors for both oncretin hormones, GLP-1 and GIP. It seems that this double action ensures a significant improvement in insulin secretion, thus improving hyperglycemia and significant weight loss. A recent publication in the prestigious medical journal NEJM for tirzepatide, a dual agonist GLP-1 and GIP, confirmed in a phase 3 study the striking effects of this innovative drug. In 40 weeks of action, he reduced the glycosylated hemoglobin (HbA1C) by 2.4% (with HbA1C at the beginning of the study 8%) and reduced his body weight to 11.4 kg “, points out Dr. Melidonis.
The side effects were only gastrointestinal side effects, so the results of the other studies to finalize these excellent actions of the double agonist are awaited with increased interest.
Also, at the European Diabetes Conferences of 2020 and 2021, the first data of phase 2 and phase 3 from an extremely innovative anti-diabetic treatment, imglimine, were presented. Imglimine acts on mitochondrial cell function: improves mitochondrial function, reduces intracellular production of toxic oxygen free radicals and increases mitochondrial biogenesis, and therefore ATP production.
All of these lead to improved tissue insulin sensitivity, decreased hepatic glucose production, and increased insulin secretion. In the studies presented, this treatment does not appear to be associated with side effects.
While in the recently published study TIMES1 it was shown, during a follow-up of 24 weeks, that imglimine significantly reduces HbA1c (0.72%).
Insulin therapy: What to expect
There are many expected developments in the field of insulin and insulin therapy. Superfast insulins (such as Aspart) have recently been added to the therapeutic reality with rapid onset and peak αυτής time after injection, which closely resembles the normal secretion and kinetics of insulin after meal, in the normal body.
In addition, studies on the efficacy and dosage of weekly insulin are in phase 3, with the help of nanotechnology testing insulin forms that will be coated with nanoparticles of polymers (and will be protected from proteolytic cleavage in the stomach) so that they can be administered mouth (per os).
Also on the rise is the history of making smart insulins that will contain a “chemical insulin transporter” that will “store” insulin in the subcutaneous tissue and release it only when the glucose concentration in the tissue increases. Thus, no continuous glucose measurement will be required and no adjustment of insulin will be required at meals. Obviously, until the final preparation of these insulins the road is long but when this is achieved the consequences will be shockingly positive.
Type 1 Diabetes: What’s new and what’s coming
The field in which there are also many new developments is the field of treatment of SD1. Developments particularly concerning pumps and the artificial pancreas
Indeed, new pumps, interconnected with glucose sensors, are now at the heart of the new treatment for type 1 diabetics. These new pumps (such as the Med 640G) have the ability to inhibit insulin delivery when level information sugar from the sensor indicate that there is a risk of hypoglycemia. This operation of the new pumps significantly reduces the risk of hypoglycemia. These new pumps have (integrated) the appropriate software so that, if the person with SD1 provides them with suitable food items, they can suggest the fast insulin units (bolus) required for the specific food.
“At the same time, we are already approaching the phase of the hybrid artificial pancreas with a very advanced glucose-software-pump sensor triad. With the hybrid artificial pancreas there will be automation in the administration of insulin between meals and fasting, while the patient’s participation will be only in meals (here lies the hybrid element), where, with the help of the pump (as described above), will regulate the insulin required on a case-by-case basis. The recently released Medronic 780G pump seems to meet many of the above requirements.
With this data it becomes obvious that we are approaching at full speed to the “integrated closed circuit”, the artificial pancreas in which the software will be additionally integrated and algorithms for the various meals, so that there is complete automation of operation and insulin delivery by the pump 24 hours a day.
This is a shocking development, as what until recently was a plan is being prepared to become a reality “, concludes Dr. Melidonis.
Writes:
Dr. Andreas Melidonis, Pathologist – Diabetologist,
Coordinating Director of the Diabetological – Cardiometabolic Center of the Metropolitan Hospital
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