[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]