Treatment of Hyperglycaemia with Oral Antidiabetic Agents in Patients with Type 2 Diabetes - Part 4, by Sten Madsbad

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From the course by University of Copenhagen

Diabetes - a Global Challenge

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University of Copenhagen

Diabetes - a Global Challenge

348 ratings

Diabetes and obesity are growing health problems in rich and poor countries alike. With this course you will get updated on cutting-edge diabetes and obesity research including biological, genetic and clinical aspects as well as prevention and epidemiology of diabetes and obesity. All lectures are provided by high-profile scientists from one the world's leading universities in diabetes research. This course is part of the EIT Health Campus programme. We hope you will enjoy our course. Best Wishes Jens Juul Holst, Signe Sørensen Torekov and Nicolai Wewer Albrechtsen Department of Biomedical Sciences Novo Nordisk Foundation Center for Basic Metabolic Research Faculty of Health and Medical Sciences University of Copenhagen

From the lesson

Clinical manifestation of Diabetes and Treatment

We hope that you enjoyed the previous modules about glucose regulation and incretin biology though they may seem more advanced compared to the first modules. We hope you stay with us and learn more about Clinical Manifestation of Diabetes and Treatment by Professor Allan Vaag and Treatment of Hyperglycemia by Professor Sten Madsbad.

Treatment of Hyperglycaemia with Oral Antidiabetic Agents in Patients with Type 2 Diabetes - Part 1, by Sten Madsbad14:15

Meet the Instructors

Jens Juul Holst
Professor, MD, DMSc
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research
Signe Sørensen Torekov
Associate Professor, MSc, PhD
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research
Nicolai Jacob Wewer Albrechtsen
MD, GCSRT, PhD student
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research

[MUSIC]

SGLT-2 inhibitors are Sodium-glucose cotransporter 2 inhibitors,

or also named Sodium-glucose linked transporter 2 inhibitors.

Normally about 180 gram of glucose is filtered through the kidney per 24 hours.

90% is reabsorbed in the proximal tubule via the SGLT-2 cotransporter.

But the last 10% is reabsorbed, via the SGLT-1 cotransporter,

resulting in that in glucose tolerant people the free of glucose.

By blocking the SGLT-2 cotransporter, the patient will

display about 60 to 70 grams of glucose for 24 hours.

Resulting in a loss of about 240 to 280 calories.

Which explains that patient with treatment of the SGLT-2 inhibitor lose weight,

but also the improvement in glucose control.

At present, three SGLT-2 inhibitors have been approved: Dapa,

Empa and Canagliflozin for clinical use in patients with Type 2 diabetes.

Since it's SGLT-2 inhibitors has a mechanism of action independent of beta

cell function and insulin resistance.

They can be used in the treatment algorithm along or

in combination with all other, all anti-diabetic agents or with insulin.

Adding a DPP-4 inhibitor or

SGLT-2 inhibitor to Metformin has been compared, in clinical trials.

After one year treatment, the reduction in Hemoglobin A1c was

better with a SGLT-2 inhibitor compared with Sitagliptin.

If we look at the weight regulation, the patient treated with the SGLT-2 inhibitor,

have on the average, lost about 2.3 kilo in weight.

While the DDP-4 inhibitor was weight neutral.

In another study, the SGLT-2 inhibitor was compared to Sulfonylurea.

During the first year follow up, the Sulfonylurea treated group displayed

the best degree of control but thereafter, the patient

treated with a SGLT-2 inhibitor was better regulating doing the four years follow up.

[SOUND] In the lower part of the slide, it is illustrated that

Sulfonylurea treatment results in a weight gain of 0.7 kilos while

the SGLT-2 inhibitor treated patient lost about 3 kilos in weight.

The SGLT-2 inhibitor also have a minor effect on blood pressure,

as illustrated in the present study.

Where treatment with Dapagliflozin resulted in a reduction in systolic blood

pressure of about 3 millimeters compared to Sulfonylurea treatment.

You have to realize that the effect of SGLT-2 inhibitors depends on

kidney function.

And therefore, SGLT-2 inhibitors should not be used in patients

with an estimated GFR less than 45 milliliters per minutes.

The effect on Hemoglobin A1c is minimal or absent and

most recommendations is that it should not be used in patients with

an estimated GFR below 60 milliliters per minutes.

Treatment with SGLT-2 inhibitors is related to

an increased risk of genital and urine and

infections explained by the increase of glucose in the urine.

About 10% of men treated with Canagliflozine will develop a mycotic

genital infection during one year treatment.

The risk of genital infection is even higher in female and

is about 14 to 15% during the first year of treatment.

Also, the risk of urinary infection is increased in females.

We can summarize about the SGLT-2 inhibitors.

The reduction in Hemoglobin A1c is about 0.6 to 2.7%,

dependent on the basal Hemoglobin A1c.

Weight loss is about 2 to 4 kilos and

the reduction in blood pressure is 2 to 5 millimeters.

Now, there is an increase risk of urine infection and genital infection.

The effect of the drug is independent of duration of diabetes,

beta-cell function and insulin resistance.

And also that the SGLT-2 inhibitors can be combined with all other

antidiabetic agents.

Type 2 diabetes is a progressive disease and

in most patient it will be necessary to combine more than two anti-diabetic

agents to control hypoglycemia or to initiate insulin treatment.

There exists, as you can understand, a lot of possibility to combine drug but

you also have to realize that you can only combine

drugs with complimentary mechanism of action on glucose metabolism.

Therefore, you should never combine the DPP-4 inhibitor to the DDP-1

receptor agonist.

And many patients today are treated with three or

even four anti-diabetic agents to obtain the glycemic targets.

About to obtain the glycemic target the thumb rule is that

anticification of treatment should be performed when

Hemoglobin A1c is more than 0.5% from the targets,

then you have to add on a new drug or initiate insulin treatment.

In relation to always an obese patient,

remember that some drug may cause weight gain, Sulfonylurea, Insulin and Glitazone.

Metformin or DPP-4 inhibitors are weight neutral.

Whereas GLP-1 receptor agonists and SGLT-2 inhibitors promote weight loss.

Remember also that in patients with impaired renal functions,

Metformin can induce lactate acidosis.

Be cautious with Sulfonylurea because of the risk of hypoglycemia.

DPP-4 inhibitors should be dose adjusted, except for Linagliptin.

Avoid use of GLP-1 receptor agonists, if GFR is below 30 milliliters per mi,

minutes, and avoid SGLT-2 inhibitors if GFR is below 45 milliliters per minute.

To summarize the key points in relation to treatment of hypoglycemia

in patients with Type 2 diabetes.

Remember that glycaemic targets and

glucose lowering therapies must be individualized.

And also that diet, exercise, and

education are still the foundation of any treatment program.

And also that unless contraindicated, Metformin is the optimal first line drug.

And lastly that all treatment decisions should be made in

conjunction with the patients.

[MUSIC]

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